Male Cousins Research Articles

Genetic predisposition to vaccine-induced immune thrombotic thrombocytopenia: is there a family link?

Background: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare life-threatening thrombotic reaction to COVID-19 vaccines. Case description: Two young male first cousins, with a family history of idiopathic thrombocytopenic purpura, developed VITT after the Ad26.COV2.S vaccine. Both had a favourable clinical and analytical outcome. We investigated the genetic factors that could be associated with a genetic predisposition to VITT. Conclusions: There are no published cases where the VITT patients were relatives. The genetic study did not reveal any likely pathogenic variants, although the prevalent polymorphism c.497A>G (p.(His166Arg)) in the FCGR2A gene was found in a homozygous state. More studies are required to better understand VITT’s pathophysiology and any underlying genetic predispositions.

Genotype-phenotype analysis of Fabry disease caused by GLA gene variation in a pedigree

Objective: To investigate the clinical phenotype and genetic characteristics of patients with Fabry disease caused by a GLA variant, IVS4+919G>A. Methods: It was a prospective study. Fabry disease screening was conducted among high-risk population in Ninghai from October 2021 to August 2023. Those children with decreased α-galactosidase enzyme activity<2.40 μmol/(L·h) or elavated Lyso-GL-3 level>1.10 μg/L in dried blood spot (DBS) method underwent GLA genetic testing for diagnosis confirmation. Meanwhile, family screening was carried out. A proband and his family members diagnosed with Fabry disease were research subjects. The clinical and genetic characteristics of patients with Fabry disease caused by the GLA variant (IVS4+919G>A) were analyzed. Results: The female proband aged 9.8 years with pain in both lower limbs as the initial symptom was found to have a heterozygous GLA variant IVS4+919G>A among 102 patients. In family screening, there were 4 family members (proband's father, elder sister, elder male cousin and elder female cousin) with Fabry disease and a family member (proband's fifth aunt) with a GLA variant. Among these 4 diagnosed family members, the elder male cousin of the proband, a boy aged 13.2 years had a heterozygous GLA variant, IVS4+919G>A with intermittent pain in both lower limbs as the initial symptom. The proband's father had knee joint pain. The proband's elder sister had decreased vision and his elder female cousin had no obvious symptoms. The proband's fifth aunt with a GLA variant had decreased vision. Conclusions: High-risk screening in children and family screening are helpful for early diagnosis and treatment of Fabry disease. Neuropathic pain may be a early symptom in children with Fabry disease caused by the GLA variant, IVS4+919G>A.

Familial cases with adult-onset FGF23-related hypophosphatemic osteomalacia -A PHEX 3’-UTR change as a possible cause-

Excessive actions of FGF23 cause several kinds of hypophosphatemic rickets/osteomalacia. It is possible that there still remain unknown causes or mechanisms for FGF23-related hypophosphatemic diseases. We report two male cousins who had been suffering form FGF23-related hypophosphatemic osteomalacia. Sequencing of exons and exon-intron junctions of known causative genes for FGF23-related hypophosphatemic diseases and whole genome sequencing were conducted. Luciferase assay was used to evaluate the effect of a detected nucleotide change on mRNA stability. Two cousins showed hypophosphatemia with impaired proximal tubular phosphate reabsorption and high FGF23. Serum phosphate of their mothers was within the reference range. Exome sequencing of the proband detected no mutations. Whole genome sequencing of the patients and their mothers identified a nucleotide change in the 3’-UTR of phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) gene (c.*1280_*1287dupGTGTGTGT) which is heterozygous in the mothers and hemizygous in the patients. While sixteen is the most prevalent number of GT repeats, this family had twenty repeats. Luciferase assay indicated that mRNA with 3’-UTR of PHEX with 20 GT repeats was more unstable than that with 16 repeats. Sequencing of exons and exon-intron junctions of known causative genes for FGF23-related hypophosphatemic diseases cannot identify all the genetic causes. Our results strongly suggest that changes of PHEX expression by a nucleotide change in the 3’-UTR is a novel mechanism of FGF23-related hypophosphatemic osteomalacia.

BIAK LANGUAGE GREETINGS AND THEIR IMPLICATIONS FOR LOCAL LANGUAGE LEARNING IN SCHOOLS

The objectives of this research are to describe Biak language greeting words in terms of form and meaning and their implications for local language learning in schools. The method used in this research is descriptive qualitative method. To collect data, the techniques used are observation, listening technique and conversation technique. To analyze the data, the technique used is qualitative analysis technique which includes: 1) Data reduction, namely simplifying the data that has been collected. 2) Presentation of data, namely, presenting data before being simplified through data grouping. 3) Verification, namely checking the accuracy of the data that has been presented. Conclusion, namely drawing conclusions to answer research questions. The results showed: 1) Family greetings: kamam (father), awin (mother), ɛba (brother), ɛknik (younger brother); 2) Kin greetings: mansar (grandfather), insar (grandmother), mɛ (aunt), kabor (nephew), insos (niece), ɛbaya kabor (male cousin), ɛbaya insos (female cousin); 3) Non-relative greetings: /ambɛr beba/ someone who has a position and is older, younger, and so on, /manan wir (community leader), manan wir bɛba (traditional leader). 4) Common greetings: kamam (father), awin (mother), kabor (a man of the same age or younger), insos (a woman of the same age or younger). The implication of this research can be applied in local language learning in schools to better understand and appreciate local culture and grammar.

Grandsons of Grandfather Fyodor Nechaev: Pedigrees of Intelligence in the Field of Genealogy of F. M. Dostoevsky (from the Additions to “The Chronicle of the Generations of Dostoevskys”)

The article presents the results of archival research devoted to the study of the Moscow branch of the family tree of Fyodor Mikhailovich Dostoevsky. The object of consideration was the generation of the grandchildren of the grandfather of the writer Fyodor Timofeevich Nechaev: the Dostoevskys (the children of Maria, his daughter from his first marriage), the Shers and the Stavrovskys (the children of the daughters of F. T. Nechaev from his second marriage — Olga and Ekaterina). Biographical data about the relatives and cousins of F. M. Dostoevsky were extracted from parish and consistory metric books stored in the Central State Archive of the City of Moscow. With a few exceptions (Mikhail, Andrey), metric records of the birth of the writer's siblings are being introduced into scientific circulation for the first time; in some cases, archival documents allowed correcting inaccuracies that were present in the biographical literature about Dostoevsky. Of the thirteen Sher brothers and sisters, male and female cousins of the writer, the names of seven were not previously mentioned even in the fundamental “Chronicle of the Generations of Dostoevskys” (2012). Of the seven Stavrovsky brothers and sisters, two were also named for the first time. Metric birth records are provided for all twenty of these relatives of Dostoevsky; for those who died in infancy, there are also death records. In four cases, the article published metric records of the wedding of the writer’s male and female cousins. In conclusion, the importance of biographical information about the Shers and the Stavrovskys is emphasized for the study of such an important event in the life of F. M. Dostoevsky in the 1870s, as was the litigation over the inheritance of A. F. Kumanina, the writer's mother's sister and half-sister of Olga Sher and Ekaterina Stavrovskaya (the so-called “the Kumanin heritage case”).

Molecular genetic characteristics of a family which coinheritance of rare-88 C>G (HBB:c.-138 C>G) β-thalassemia mutation with α-thalassemia and review of the literature

The molecular genetic characteristics of a family with rare -88 C>G (HBB: c.-138 C>G) β-thalassemia gene mutation were studied using cohort study. The cohort study was conducted from June to August 2022 by Prenatal Diagnosis Center of Sanya Women and Children's Hospital Managed by Shanghai Children's Medical Center. The phenotype and genotype were analyzed by hematological cytoanalyzer, automatic electrophoretic analysis system, and next-generation sequencing (NGS). And then, Sanger sequencing was used to verify the rare gene results. The results showed that the proband, her father, her uncle and her younger male cousin had discrete microcytosis (MCV 70.1 fl, 71.9 fl, 73.1 fl and 76.6 fl, respectively) and hypochromia (MCH 21.5 pg,22.0 pg,22.6 pg and 23.5 pg, respectively), elevated hemoglobin A2 level (5.3%, 5.4%, 5.4% and 5.5%, respectively), slightly elevated or normal fetal hemoglobin (Hb F), but no anemia. The proband was identified to have co-inherited ɑ-thalassemia (Hb Westmead gene heterozygous mutation, ɑwsɑ/ɑɑ) and β-thalassemia with a rare -88 C>G (HBB: c.-138 C>G) heterozygous mutation (β-88 C>G/βN). Her mother had the same α-thalassemia as the proband. Her father, her uncle and her younger male cousin had the same rare -88 C>G heterozygous mutations as the proband. While her grandmother and younger brother were not carrier of thalassemia. In conclusion, 4 cases of rare -88 C>G(HBB:c.-138 C>G) heterozygous mutation had been detected in a Chinese family. Carriers of this beta-thalassemia are clinically asymptomatic. This study enriches the knowledge of the thalassemia mutation spectrum in Chinese people and provides valuable information for genetic counseling, prenatal diagnosis, and prevention of thalassemia, providing a scientific basis for improving the quality of birth population and preventing birth defects.

Konjenital Ağrı Duyarsızlığı ile Anhidrosis Sendromu: Diyala vilayeti / Irak’tan Bir Olgu Sunumu

Congenital insensitivity to pain with anhidrosis syndrome (CIPA); is a rare autosomal recessive disorder presenting with pain insensitivity, sweating inability, and intellectual disability. The incapability to sense pain and temperature often leads to recurrent severe and inadvertent self-inflicted harm; these can result in severe complications, as patients settle slowly from skin and bone harm. We present a case of a four-year-old boy with a diagnosis of CIPA, after repeated visits to the hospital emergency department for repeated chest and both ankle joint infections, which prompted further investigations. Case report A four-year-old boy was admitted to Albatool teaching hospital for maternity and children in Baqubah, Diyala, Iraq because of recurrent chest and both ankle joints infection. He is the second child of consanguineous parents. His six-year-old sister is normal. The mother noticed early after birth that her child was suffering from high fever, he was not responding to pricking and injections, and he never sweats with intolerance to warm weather. Examination revealed mental developmental delay, absent upper and lower canine teeth, napkin and face dermatitis which was intractable to therapy, and deep pus discharging ulcers of both heels. Radiology of feet shows signs of osteomyelitis. There is a history of the same disease in two male cousins who died at age of three and five years respectively, the overall clinical context warranted a clinical suspicion of CIPA. Early diagnosis of this extremely rare disease is very important for the treatment and prevention of complications. Conclusion: This case report shows that a clinician should suspect to investigate for CIPA when managing kids with multiple inadvertent self-inflicted harms, anhidrosis, and pain insensitivity.

MEHMO syndrome: complexity of verifying the diagnosis

MEHMO syndrome (OMIM: 300148; ORPHA: 85282) is a disease appears by mental retardation, epilepsy seizures, hypogonadism, microcephaly, and obesity. Pathology is associated with mutations in the EIF2S3 gene located on the X chromosome and leads usually to serious disability of patients. The article presents a clinical observation of the case of the syndrome in two male cousins with microcephaly, manifested by a complex of endocrinopathies (hyperinsulinemic hypoglycemia, multiple adenohypophysis hormone deficiency) and accompanied by severe neurological abnormalities (epilepsy, spastic tetraparesis, optic nerve atrophy). The complexity of the diagnostic due to the rarity of this syndrome, is described.

Limiting distribution of X-chromosomal coalescence times under first-cousin consanguineous mating

By providing additional opportunities for coalescence within families, the presence of consanguineous unions in a population reduces coalescence times relative to non-consanguineous populations. First-cousin consanguinity can take one of six forms differing in the configuration of sexes in the pedigree of the male and female cousins who join in a consanguineous union: patrilateral parallel, patrilateral cross, matrilateral parallel, matrilateral cross, bilateral parallel, and bilateral cross. Considering populations with each of the six types of first-cousin consanguinity individually and a population with a mixture of the four unilateral types, we examine coalescent models of consanguinity. We previously computed, for first-cousin consanguinity models, the mean coalescence time for X-chromosomal loci and the limiting distribution of coalescence times for autosomal loci. Here, we use the separation-of-time-scales approach to obtain the limiting distribution of coalescence times for X-chromosomal loci. This limiting distribution has an instantaneous coalescence probability that depends on the probability that a union is consanguineous; lineages that do not coalesce instantaneously coalesce according to an exponential distribution. We study the effects on the coalescence time distribution of the type of first-cousin consanguinity, showing that patrilateral-parallel and patrilateral-cross consanguinity have no effect on X-chromosomal coalescence time distributions and that matrilateral-parallel consanguinity decreases coalescence times to a greater extent than does matrilateral-cross consanguinity.

A Gendered Return

A Gendered Return

A FAMILY WITH HEREDITARY PARAGANGLIOMA SECONDARY TO SDHD MUTATION

INTRODUCTIONA third of pheochromocytoma and paraganglioma (PPGL) tumours are part of a hereditary syndrome. Hereditary PPGL shows autosomal dominant inheritance with variable penetrance. Genetic testing is recommended in all patients diagnosed with PPGL regardless of age at presentation and family history. SDHD is the most frequently mutated gene in head and neck PGLs and associated tumours have low malignancy rate. This gene is maternally imprinted with silencing of the maternal allele, thus, the risk of developing paragangliomas is limited to offsprings who inherit the pathogenic variant from their father. Paternally inherited pathogenic variants are highly penetrant by age 50. We describe a family with hereditary paraganglioma due to mutation in the SDHD gene. RESULTSThe index patient is a 23 year-old female who was diagnosed to have bilateral adrenal pheochromocytoma with carotid and cardiac paragangliomas. Genetic screening revealed that she has SDHD mutation. Further family history revealed that 2 out of 3 paternal aunts have carotid paragangliomas. Her father, youngest of 5 siblings, paternal uncle and grandfather passed away at age 42, 40, 39 years old, respectively, due to severe headache and possible haemorrhagic stroke. Six other family members underwent genetic screening as well. Five family members were positive for SDHD mutation. These include the index patient’s elder sister, 3 paternal aunts (2 with carotid paragangliomas) and one male cousin. CONCLUSIONGenetic testing for family members of patients with hereditary paragangliomas is recommended after thorough genetic counselling. Genetic testing for firstand second-degree relatives is recommended for SDHDrelated paraganglioma. Healthy asymptomatic carriers for the gene mutation should undergo clinical assessment, plasma and/or urine metanephrines and normetanephrines and a combination of whole-body MRI (head and neck, abdominal and pelvic) and PET-CT imaging at initial screening. Thereafter, recommendations for long-term surveillance include annual clinical and biochemical evaluation along with whole body MRI repeated every 2-3 years.

Delivery Planning and Emergent Neonatal Intervention in Transposition of the Great Arteries.

* Abbreviations: CICU: : cardiac intensive care unit d-TGA: : dextro-transposition of the great arteries FIO2: : fraction of inspired oxygen A 20-year-old gravida 2, para 1 pregnant woman was referred to our fetal care center because of a diagnosis of structural heart disease in the fetus. The woman’s medical history included asthma, seasonal allergies, and depression, with no surgical history. She had 1 prior term vaginal delivery. This pregnancy had been complicated by late presentation to prenatal care at 20 weeks’ gestation. Her medications included asthma maintenance medications and prenatal vitamins. Pertinent family history included her partner who had a ventricular septal defect and a paternal male first cousin with transposition of the great arteries. Prenatal laboratory test results were unremarkable and genetic screening was declined. Imaging at the referring obstetrician’s office was significant for transposition of the great arteries with an intact ventricular septum and normal fetal biometry. She was referred to our center at 21 1/7 weeks’ gestation, with imaging and consultation with fetal cardiology at 21 6/7 weeks’ gestation. The following tests were performed: Figure 1. Four-chamber view of the heart at 21 weeks’ gestation, swept to the outflow tracts showing parallel arrangement of the great arteries with the pulmonary artery (PA) located posteriorly and arising from the left ventricle (LV) and the aorta (Ao) arising from the right ventricle (RV). Fetal position: right (R), left (L), anterior (A), posterior (P). At …

Fully penetrant genetic mutation results in wide familial variability: a cardiac magnetic resonance focused report

Abstract Dilated cardiomyopathy (DCM) is a myocardial disorder characterized by ventricular dilation (LV or biventricular) and systolic dysfunction, with a broad etiological spectrum, comprising numerous genetic and non-genetic causes. Cardiac magnetic resonance (CMR) has become an important tool in guiding the etiological diagnosis in DCM. We present the case of a 37-years old man admitted to our department in order to investigate the diagnosis of DCM using CMR. Cine imaging showed mild left ventricular (LV) dilatation and moderate systolic (LV ejection fraction = 42%) dysfunction, but also apical hypertrabeculation meeting the criteria for non-compaction and late gadolinium enhancement (LGE) images revealed mid-wall fibrosis in the basal and midventricular segments of the inferior interventricular septum (IVS) – typical of non-ischemic DCM. Complete family history revealed the diagnosis of DCM in the mother of the patient and in the maternal grandfather, who had died at 87. After genetic testing of the index patient showed a pathogenic mutation in the TTN (titin) gene (c.79273A&gt;T), cascade genetic testing followed, for his mother, sister, uncle and two cousins who all came back positive for the same mutation. CMR examination of the mother done 6 years prior demonstrated severe LV dilatation and systolic dysfunction (LV ejection fraction = 23%), LV non-compaction and mid-wall IVS fibrosis. CMR examination was performed for the other members of the family and discovered pathological findings in the uncle (normal LV volume and function, but focal mid-wall fibrosis in the inferior IVS) and the male cousin (LV non-compaction), while the female cousin had a normal exam. Using CMR and genetic testing, this case report proves the phenotypic heterogenicity of a completely penetrant titin mutation in the same family. Moreover, CMR is shown to be essential in DCM evaluation, having the ability to guide etiologic diagnosis and to detect alterations such as fibrosis and non-compaction in the absence of LV dilation or dysfunction.

Under State Protection Aeschylus’ the Suppliants and the Shift from Clan to State

Aeschylos’ tragedy The Suppliantsis in this article related to an opposition between clan and state—and more specifically with the development in ancient Greece from barbarism to civilization, from a lawless, uncultivated and disorganised world, to a clan-based social order and from there to a state-based organisation, which in many ways would set the pattern for the development in Europe for centuries to come.In the play, fifty sisters are fleeing from Egypt to Argos, persecuted by their fifty male cousins. The women seek protection and therefore refer to their shared origins with the population of Argos.The fact that Danaus has fifty daughters but no son, implies that if the daughters marry their cousins the legacy will stay within the clan. What the daughters’ uncle Aegyptus and his sons demand is that Danaus and his daughters should act in accordance with the regulatory framework of the clan system. This stipulates that in cases where fathers in patrilineal systems only have daughters, these daughters must marry endogamically (that is inwards) instead of exogamic ally (outwardly, and in the corresponding way for sons in matrilineal systems).The article shows how Argos, governed by King Pelasgus, is depicted in the play in contrast to the claustrophobic catatonia of incestuous relations, the latter illustrated by an imagery that stems from archaic Greek mythology. The claustrophobic feeling that links the family and kin in The Suppliants, through events such as incestuous marriages and family-related cannibalism, gives a picture of the individual’s room for manoeuvre being strictly regulated—in fact almost non-existent—in the extended family. It is such a claustrophobic world that the women in The Suppliants (like Orestes in Oresteia) are fleeing from.Instead they seek out a city state based on fundamentally different ideas than the family, kinship and clan-related organisation principles of the Egyptians. The Greek city state thereby appears to aim to liberate the archaic human from a claustrophobic captivity.

Mulan: Five Versions of a Classic Chinese Legend, with Related Texts ed. by Shiamin Kwa and Wilt L. Idema

Reviewed by: Mulan: Five Versions of a Classic Chinese Legend, with Related Texts ed. by Shiamin Kwa and Wilt L. Idema Yining Lin MULAN: FIVE VERSIONS OF A CLASSIC CHINESE LEGEND, WITH RELATED TEXTS. Edited and Translated, with an Introduction, by Shiamin Kwa and Wilt L. Idema. Indianapolis/Cambridge: Hackett Publishing Company, Inc., 2010. 136 pp. 6 black and white photos. $36.25. The legend of Mulan, the brave and loyal girl who takes her ailing father's place in the army to fight against foreign invaders, remains one of the most popular Chinese stories. In an installment of a larger series of translations, Shiamin Kwa and Wilt L. Idema trace Mulan's story from her first appearance in two 12th century poems to the twentieth century through translations of poems and scripts along with summaries of additional plays and novels. The translations and summaries included in this book gives the reader a comprehensive idea of how Mulan, as character and prominent figure, reflected the political agendas of the time. [End Page 338] Included in this anthology are translations of "The Poem of Mulan" by an anonymous author and "Song of Mulan" by Tang Dynasty official Wei Yangfu. Both poems were a part of a 12th century anthology entitled Collected Works of the Music Bureau (Yuefu shiji) compiled by Guo Maoqian. The book also includes two translated plays The Female Mulan Joins the Army in Place of Her Father by Xu Wei in the 16th century and the anonymously authored Mu Lan Joins the Army (1903). The book's final text is a translation of a 1939 film version of Mulan's story called Mulan Joins the Army written by Ouyang Yuqian, one of the original huaju (spoken drama) playwrights and actors. While each version has a different emphasis depending on the time it was written, Kwa points out that the major plot points remain the same: Mulan's father is called up to fight, but he is elderly, so she replaces him by disguising herself as a man. She carries out this disguise for over a decade, rising in the ranks, which captures the attention of the Emperor, who rewards her with a high-ranking position in government. She refuses the position, telling the Emperor that she wishes to return home to her family. She returns home with accolades and instantly resumes her position as a filial and chaste daughter. In the introduction, Kwa explores the changing meanings behind each version of the story. In her discussion of the poems, Kwa highlights the authors' use of equipment, such as the armor, the horse, and weapons, as a way to act out the putting on of gender through clothing, noting that "when people are dressed identically, their sexuality is obscured" (p. xv). The poems end with Mulan resuming her position as the good and filial daughter by putting on her makeup and dress. Moving into the translations of the xiqu and cinematic versions of the story, Kwa notes that filial piety and loyalty to family and government become a big part of the story. In all three versions, Mulan promises her parents that she will remain chaste and manages to ingratiate herself with the men that she leads. While there is some suspicion and romantic intrigue in all three versions, Mulan's cover remains intact until the very end when she reveals herself as a woman to her closest friends and comrades. The conventions of xiqu demand that each play must have a rounded ending, or tuanyuan, where the events of the play must be resolved. In the cases of The Female Mulan Joins the Army in the Place of Her Father and Mu Lan Joins the Army, Mulan arrives home and, as in all versions of the story, is instantly married to a neighbor, Mr. Wang, and rejects her Second-in-Command Liu Yuandu, thus forming the tuanyuan. However, in the ending to the 1903 version of Mu Lan Joins the Army, the rewards that Mulan receives for her valor and bravery in the field are transferred from her to her male cousin, Mu Shu, who [End Page 339] refused to join the army at the beginning of the...

Hair Rules: Race, Gender, and Stigmatization in Schools

As laws banning racial hair discrimination in schools are proposed across the United States, it is increasingly important to understand how grooming policies can stigmatize students. This essay engages social science theory and research on stigmatization and the case of Arnold v. Barbers Hill Independent School District to investigate the cultural constructions of male students who wear long locs. Drawing on content analysis of court documents around this Texas lawsuit involving two black male cousins who were disciplined in school because of refusing to cut their locs, I examine how school officials justified the district hair rules through associating the defendants’ hairstyle with a range of stigmatizing attributes. The conclusion considers the potential for this court case, as well as proposed hair discrimination laws in Texas and other states, to mitigate the stigmatization of boys who wear long locs, long braids, and long twists. I argue that to fully address the stigmatization of boys who wear these styles, laws and policies must be attentive to race as well as gender.

Clinical and Genetic Findings in CTNNA1-Associated Macular Pattern Dystrophy

Clinical and Genetic Findings in CTNNA1-Associated Macular Pattern Dystrophy

Novel CD40LG Mutation in Two Cousins With Immunoglobulin Class Switch Recombinant Deficiency

The hyper-immunoglobulin M (HIGM) syndrome comprises a group of rare inherited immunodeficiency disorders characterized by normal or elevated levels of serum IgM with low or absent levels of serum IgG, IgA, and IgE. Patients with this syndrome usually present with a history of recurrent infections or opportunistic infections. Here, we report two male cousins from homozygote twin mothers. The first cousin presented with no signs or symptoms other than neutropenia, which was accidentally found in a routine blood test. Immunological workup in this patient showed undetectable IgG and IgA levels and normal IgM levels. The second cousin had a history of recurrent infections, and at the time of admission, he was diagnosed with Pneumocystis jirovecii infection. The immunologic workup of this patient showed undetectable IgG, decreased IgA, and increased IgM level. Due to their interesting family relationship, genetic analysis was performed, which detected a novel mutation in exon 2 (c.266 del G) of the CD40 ligand gene (CD40LG).

MON-076 Adrenal Hypoplasia Congenita - Is It Possible to Make This Diagnose in Previous “Idiopathic” Adrenal Insufficient Patients? Series of Cases

Background: Adrenal hypoplasia congenita (AHC) is a rare disease (1:70.000 men) characterized by reduction in all cortical adrenal hormones and also by hypogonadism. NR0B1 -related AHC includes both X-linked AHC and Xp21 deletion. AHC gene mutation was first described in 1994 and occurs in less than 1% of adrenal insufficiency (AI) cases and it is imperative that clinical endocrinologists increase their knowledge on this condition to recognize it as promptly as they were used to do so in other causes of pediatric AI.Clinical Cases: We describe here two sporadic cases and three familial cases from one family, all of them attending at our Endocrine Unit at HCPA, in the South of Brazil. The median age of AI first symptoms was 1 month old in two patients (acute infantile onset due to a salt wasting crises), and eleven years old in the remaining patients (childhood onset). Their exams confirmed the clinical suspicion of primary AI because of low plasma cortisol (from < 0.5 to 4 mcg/dl - reference range from 7-24 mcg/dl), as well as all adrenal steroids levels, high ACTH levels (from 672 to 2225 pg/ml - reference range from 7-63 pg/ml) and high plasmatic renin (from 92 to 448 mcUI/ml - reference range from 2.8-39.9 mcUI/ml). They were also extensively investigated searching for the AI pathophysiology. After some years of lost follow-up, one of the familial cases that had first been seen in 1993, returned to our hospital and was diagnosed with hypogonadism, leading to NR5OB1 gene evaluation.Regarding the genetic etiology, one of the sporadic cases developed a clinical picture including profound developmental delay, seizures and strabismus suggestive of a contiguous gene syndrome that involves Duchenne muscular dystrophy, glycerol kinase deficiency and AHC. A CGH array was performed and identified a Xp21.3-p21.1 deletion. The affected family had an extensive history suggestive of a genetic disease with X-linked inheritance pattern, as shown by the premature death of 3 uncles and a male cousin. A deleterious variant (c.131_212delinsTGAGACCTGTACCGT) in NR5OB1 gene was identified by Sanger sequencing in hemizygous state in the 46,XY affected patients.Conclusion: Albeit a rare disease, it is crucial that endocrinologist all around the World could be aware about clinical characteristics of this condition in order to properly diagnose it. And it is even possible, as it occurred with one of our patient, to make a late pathophysiologic diagnosis, making possible to treat the associated hypogonadism. Reference: Acherman JC, Vilain EJ. NR0B1- related adrenal hypoplasia congenita. GeneReviews 1993-2019.

Hawaiian by Birth: Missionary Children, Bicultural Identity, and US Colonialism in the Pacific by Joy Schulz

Reviewed by: Hawaiian by Birth: Missionary Children, Bicultural Identity, and US Colonialism in the Pacific by Joy Schulz Clifford Putney Hawaiian by Birth: Missionary Children, Bicultural Identity, and US Colonialism in the Pacific. By Joy Schulz. Lincoln: University of Nebraska Press, 2017. xii + 222 pp. Cloth $49.98. In Hawaiian by Birth, Joy Schulz sheds new light on a remarkable group of individuals: the children of the first Christian missionaries in the Hawaiian Islands. Much has been written about the missionaries (who radically transformed the islands in the early to mid-1800s), but less has been written about their children, who called themselves the Cousins. Many of the Cousins made large fortunes in Hawai‘i, and they participated in the overthrow of the native Hawaiian monarchy in 1893. The Cousins did a great deal as adults, but Schulz is primarily interested in what they did (and what was done to them) in their childhood and youth. Schulz did an enormous amount of archival research at mainland US institutions such as Williams College (a magnet for male Cousins) and Mt. Holyoke College (a magnet for female Cousins). She also delved deeply into the archives of Hawaiian institutions such as the Hawaiian Mission Children’s Society (which the Cousins founded in 1852 to evangelize Polynesia) and Punahou School (which was founded in 1841 to educate the Cousins). In the latter institution (Barack Obama’s alma mater), Schulz combed through a treasure trove of material that the Cousins (an exceptionally literate bunch) wrote as children, and she draws heavily on that material. Schulz is an excellent scholar, and she provides us with the best available account of the Cousins’ early years. Her work is insightful and comprehensive, [End Page 155] but those who have not read it might ask, why should we care about the Cousins? In answer to this question, many people contend that the Cousins are unworthy of attention. Hawaiian nationalists in particular think poorly of the Cousins, whom they dismiss as greedy white imperialists. That most of the Cousins were imperialists (at least with regard to Hawai‘i) cannot be denied, but Schulz argues persuasively that they should not be treated as cartoonlike villains, and she describes them as a useful “lens through which to understand American imperialism in the Pacific” (11). Schulz focuses on why the Cousins became imperialists. She allows that their imperialism was based in large part on economics and notions of white supremacy, but she also asserts that the Cousins developed a fierce love of the Hawaiian land (‘āina) when they were children, and that they came, arrogantly but sincerely, to view themselves as the best custodians of the land. Unlike their parents (the missionaries), the Cousins did not think of themselves as foreigners in Hawai‘i. Instead, they thought of themselves as Hawaiians of American descent, and they cited patriotism as a reason for wresting control of Hawai‘i away from a native monarchy that they viewed as corrupt. The Cousins were complex individuals. On the one hand they tended to be paternalistic, if not racist, but on the other hand they tended to be progressive with regard to slavery, women’s rights, and a host of other issues. Because of their complexity (not to mention their historical significance), the Cousins cry out to be analyzed, and Schulz does just that, methodically examining the forces that shaped the missionary children. In the first chapter of her book, Schulz concentrates on the Cousins’ parents, the missionaries. Agents of the American Board of Commissioners for Foreign Missions (the country’s first sponsor of overseas missions), the missionaries (most of whom were New England Congregationalists) showed real courage in voyaging around the world to live in Hawai‘i, and the Cousins admired them for that. The Cousins did not, however, relish the strict Calvinism under which they were raised. Nor did they like having their parents leave them alone to go off proselytizing. The Cousins experienced a childhood that was both wonderful and terrible. While they got to go swimming, spelunking, and horseback riding in Hawai‘i (one of the most beautiful places on earth), they also had to endure the confines of Punahou, which was as...