Sex-linked Recessive Inheritance Research Articles

Multiple Cervical Root Resorption Involving 22 Teeth: A Case with Potential Genetic Predisposition

A rare case of extensive multiple idiopathic cervical root resorption with potential genetic predisposition was presented. A heathy 19-year-old Chinese male with no contributory medical or family/social history complained of pain during mastication that lasted for several months. Oral examination identified 7 missing teeth and external cervical root resorption involving 9 teeth. Comparison of orthopantomograms taken in May 2021 and February 2022 identified that cervical root resorption occurred in 22 teeth. Resorption commenced at the cementoenamel junction and progressed rapidly over the 9-month period. Laboratory test results were within normal limits. Trio-based whole-exome sequencing showed a missense mutation c.5630 C > T in the filamin A (FLNA) gene at chromosome X of the subject. This is suggestive of the possibility of sex-linked recessive inheritance. This is the first study to report FLNA mutation in human subjects with cervical root resorption involving multiple teeth.

English

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common worldwide enzymopathy with approximately 400 million individuals affected. This inherited disease is sex-linked recessive inheritance. The high prevalence of certain variants of G6PD in different populations and ethnic groups increases the likelihood of finding associations with other pathologies. Sickle cell disease and thalassemia are the most common pathologies associated with G6PD deficiency. The aim of this study was firstly to study the prevalence of glucose-6-phosphate dehydrogenase deficiency (A-376/202) by molecular analysis in homozygous sickle cell patients, and secondly to study the influence of this association on the clinical severity of the disease. In a cross-sectional study, 100 patients aged 15 years with homozygous sickle cell disease in the stationary phase regularly monitored in a National Center for Blood Transfusion were included over a six-month period stretching from September 2015 to February 2016. An EDTA sampling tube was taken from each patient for the study of hematological parameters and a molecular study for the detection of mutations 376 and 202. Clinical, epidemiological and biological variables were collected using a questionnaire. Data was analyzed using Epi-info 7.2. The results of the study showed that the variant A- characterized by a double mutation (376/202) was found with a frequency of 13% (13/100) with a clear male predominance (p E‚ 0.006). Variant A- was statistically significantly associated with cholelithiasis (pE‚0.031). This study is of therapeutic interest since the recognition of G6PD-deficient sickle cell disease would make it possible to take adequate preventive measures with respect to the taking of oxidizing drugs. Key words: Glucose-6-phosphate dehydrogenase (G6PD) deficiency, sickle cell disease, stationary phase, Senegal.

Analysis of inconsistencies in terminology of spinal and bulbar muscular atrophy and its effect on retrieval of research

Diseases are sometimes known by many names 1–9, which complicates the retrieval of publications. Rare and emerging diseases may be especially vulnerable to this. Health sciences librarians do not often encounter rare diseases and may be unaware of the search challenges that these diseases present. To effectively retrieve publications for research, a strategy to identify all the different names of a disease is needed so that these can be incorporated into a comprehensive search. The author was engaged in a research project to create a comprehensive bibliography of the rare disease spinal and bulbar muscular atrophy (SBMA). The project utilized a strategy to identify all of the various names for the disease. This strategy should be helpful not only for SBMA researchers, but for anyone interested in a methodology for obtaining a comprehensive list of names for a disease. Spinal and bulbar muscular atrophy (SBMA) SBMA (ORPHA481, OMIM #313200, SNOMED CT Concept ID 230253001†) is a rare progressive neuromuscular disorder of males marked by proximal muscle weakness, cramping, fasciculations (twitching of individual muscle fibers), and muscle atrophy. Symptoms have been reported to first begin to develop between the third to sixth decades of life. Prevalence of SBMA has been reported alternately as 1 in 40,000 10, 1–2 in 100,000 11, and less than 1 in 50,000 live male births 12, but it is thought to be underdiagnosed 13–15. Degeneration of anterior horn cells (lower motor neurons) in the spinal cord of affected individuals is observed. Additional symptoms may include gynecomastia (abnormal growth of breasts in males), testicular atrophy, dysarthria (difficulty speaking), and dysphagia (difficulty swallowing). At this time, there is no known cure for most such neuromuscular diseases 16. Inheritance of SBMA is by traditional X-linked genetics. The disorder is related to a genetic defect in which a trinucleotide repeat occurs in the first exon of the androgen receptor gene on the X chromosome, first identified by La Spada in 1991 17. The string of three nucleotides of a trinucleotide repeat is present in a normal gene but is an unusually long string in a defective gene. The trinucleotide repeat of SBMA is cytosine-adenine-guanine (CAG), which codes for the amino acid glutamine. The presence of the repeat in DNA translation results in a string of glutamine molecules in the resulting peptide. Normal CAG repeat length in the androgen receptor gene is 11–34. SBMA is diagnosed if the number of CAG repeats exceeds 38 18, 19. Women do not develop SBMA, but heterozygous and homozygous women may exhibit mild symptoms, particularly muscle twitching and cramping 13, 20, 21. SBMA was identified as a unique disorder in 1968 by William R. Kennedy, but the disorder existed before its discovery 22. As far back as 1897, Japanese neurologist Hiroshi Kawahara first described what appeared to be SBMA in two brothers suffering from muscle atrophy and fasciculation of the tongue and limbs, with adult onset and sex-linked recessive inheritance 23, 24. Several disorders of varying severity and outcomes resemble SBMA, and the disorder is thought to be frequently misdiagnosed 25–29. The most well known is amyotrophic lateral sclerosis. The most challenging are the spinal muscular atrophies (SMA). However, SMA is an autosomal recessive genetic disease. Symptoms of most forms of SMA arise in childhood, but SMA3 is suggested to possibly first appear in adolescence or young adulthood. SMA4 symptoms may appear after age 30 30.

The prune belly syndrome: report of a rare case and review of literature

The prune belly syndrome (PBS) is a rare birth disorder characterized by three major findings: a variable aplasia of the abdominal wall, urinary tract malformations, and cryptorchidism [1–3]. The syndrome was first described by Frolich in 1839 [1], but it was not until 1901 that the condition was named by Osler [2]. The syndrome got its descriptive name due to the wrinkled abdominal skin (the intestinal pattern is evident through the thin, lax abdominal wall) that resembles a dried prune. Synonyms are the Eagle–Barrett syndrome, the Obrinsky syndrome, and the triad syndrome [4–6]. The disease occurs in 1:40,000 to 1:30,000 live births and only 50% of the infants survive their second birthday [7, 8]. Approximately 97% of the prune belly patients are males, and remarkably 4% of all the cases are twin pregnancies [8–10]. The etiology is still a point of debate, but there is a strong belief that the disease has a sex-linked autosomal recessive inheritance due to the male preponderance of PBS [10, 11]. When the syndrome is expressed in females, it is called the pseudo-prune belly syndrome [9]. An association with trisomy 18 and 21 has been described [12]. In 1903, in making an attempt to explain the pathophysiology, Stumme [3] suggested an in utero obstruction of the urinary tract causing a dilatation of the bladder and, secondary to this situation, a pressure atrophy of the abdominal muscles. Although very plausible, his theory was countered by histopathological investigation of the abdominal wall which revealed that there was no atrophy but rather a developmental arrest of the muscle. A more recent theory is that of a mesenchymal development arrest between the sixth to tenth week of gestation [6, 13]. This could also explain the involvement of the genitourinary tract and testis. Histopathological findings confirm that there is a mesodermal differentiation problem (abundance of collagen, fibrous, and connective tissues, rare presence of smooth muscles throughout the urinary tract) rather than one of obstruction. In the past, the treatment of PBS was almost exclusively focused on the urinary tract problems and the cryptorchidism [6, 14, 15]. The abdominal problems were of less importance and solved by the use of bandages and corsets. More recently, in cooperation with the pediatric urologist, the plastic surgeon performs abdominal wall reconstructions for both cosmetic/psychosocial and functional reasons [16–21]. The techniques used for these reconstructions can be divided into two major groups: the plication technique and the muscle transposition technique. The plication technique was first used by Duckett [18] in 1976 in order to improve the cosmetic and psychosocial situation of the patient. In 1981, Randolph [16] described an excision of the lower part of the abdominal wall in patients with remnants of muscle in the upper and lateral abdominal wall. This procedure, however, led to lateral bulging in most of the cases. Ehrlich [17] (1986) performed a more extensive technique: through a midline incision, he constructed a double musculo-fascial layer, using the hypoplastic remnants of the abdominal wall. Afterward, the redundant skin was excised. Montfort [18] modified this K. Verdonck (*) :G. Van Eeckhout : P. Wylock Department of Plastic, Reconstructive and Aesthetic Surgery, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium e-mail: kristoffverdonck@hotmail.com

Problem-solving test: A mutation causing cystic fibrosis

Terms to be familiar with before you start to solve the test: cystic fibrosis, pedigree analysis, transmembrane protein, channel protein, polymerase chain reaction, primers, polyacrylamide gel electrophoresis, fluorescent DNA staining, autosomal vs. sex-linked inheritance, recessive vs. dominant inheritance, homozygote, heterozygote, frame-shift mutation, deletion.

Primary megalocornea: clinical features for differentiation from infantile glaucoma.

To describe the ocular findings in megalocornea to assist in its differentiation from infantile glaucoma in the evaluation of children with abnormally enlarged corneas. The clinical findings of 4 boys found to have megalocornea following referral for evaluation of large corneas and suspected glaucoma were reviewed. Three of the 4 patients had photophobia. Clear and enlarged corneas were observed associated with deep anterior chambers, posterior bowing of the irides, and normal intraocular pressures (IOPs) in all eyes. Transillumination of the irides was found in 6 of 8 eyes and pigment dispersion was seen in 4 of 8 eyes. Pigment dispersion appeared to be acquired over time, and the youngest patient in this series who had pigment dispersion detected on slit-lamp examination was 15 years; the youngest patient with the condition detected on gonioscopy was 8 years. No breaks in Descemet's membrane were present. Family history obtained from 3 of the 4 patients revealed evidence of sex-linked recessive inheritance. These findings are distinct from the clinical features of infantile glaucoma characterized by elevated IOP, breaks in Descemet's membrane, corneal edema, a generally flat iris profile, less pronounced enlargement of the anterior segment, the absence of iris transillumination and pigment dispersion, and autosomal recessive inheritance. Three patients had corneal size asymmetry, a finding that has not been previously reported. Hereditary megalocornea has defining clinical findings that help to identify and differentiate it from other causes of enlarged corneas. Asymmetry in corneal size does not preclude its diagnosis.

Criterion for Fetal Primary Spongiform Cardiomyopathy

BACKGROUND Most cardiomyopathies recognizable in utero are the dilated type—with dilated, poorly contractile left ventricle. We propose a diagnostic criterion for the rare spongiform (noncompacted) cardiomyopathy. CASES Three perinatal cases with echocardiography and autopsy are presented. The apical ventricular myocardium was thickened and markedly trabeculated. The ventricles were not dilated in two, and the atria were enlarged in all. Hydrops and bradycardia were present in all three despite normal or only mildly diminished contractility. Although the cardiomyopathy was familial in two siblings, two of three cases were female, ruling out Barth syndrome (with sex-linked recessive inheritance). Although all three of our cases with hydrops died, rare survivors have been reported in the eighth decade. CONCLUSION Although spongiform cardiomyopathy may eventually develop into a dilated cardiomyopathy, its early characteristic is relatively diagnostic: a restrictive cardiomyopathy with no enlargement of the ventricles and prominent atria.

Criterion for fetal primary spongiform cardiomyopathy: restrictive pathophysiology

BACKGROUND: Most cardiomyopathies recognizable in utero are the dilated type—with dilated, poorly contractile left ventricle. We propose a diagnostic criterion for the rare spongiform (noncompacted) cardiomyopathy. CASES: Three perinatal cases with echocardiography and autopsy are presented. The apical ventricular myocardium was thickened and markedly trabeculated. The ventricles were not dilated in two, and the atria were enlarged in all. Hydrops and bradycardia were present in all three despite normal or only mildly diminished contractility. Although the cardiomyopathy was familial in two siblings, two of three cases were female, ruling out Barth syndrome (with sex-linked recessive inheritance). Although all three of our cases with hydrops died, rare survivors have been reported in the eighth decade. CONCLUSION: Although spongiform cardiomyopathy may eventually develop into a dilated cardiomyopathy, its early characteristic is relatively diagnostic: a restrictive cardiomyopathy with no enlargement of the ventricles and prominent atria.

Genetic analysis of triploidy in a selected line of chickens.

We investigated the pattern of inheritance of maternal meiotic errors responsible for a high frequency of triploid progeny in a selected line of chickens. For the genetic analysis, F1 and backcross populations were produced from crosses between normal diploid individuals of the triploidy line and a control line. Triploid embryos were produced by 35% and 67% of reciprocal F1 females and by 24% and 67% of reciprocal backcross females. These results exclude autosomal recessive and sex-linked recessive or sex-linked dominant inheritance. A single autosomal dominant gene is also not likely to be responsible. However, the results are consistent with the determination of triploidy by a single autosomal gene with no dominance, and an even better fit is obtained by two loci, an autosomal gene with no dominance and a sex-linked gene. The results cannot exclude a multifactorial mode of inheritance, but the rapid response to selection for triploidy and consistent expression of the meiotic errors in different genotypes suggest that meiotic mutations at one or two loci are the most plausible genetic basis for the trait.

Hereditary vasopressin resistance in man and mouse.

The DI +/+ Severe hereditary nephrogenic diabetes insipidus mouse is resistant to the antidiuretic action of vasopressin (VP) because of failure to accumulate cAMP and subsequent inability to form intramembranous particles on the apical (luminal) surface of kidney cells that normally respond to VP. The defect is primarily, if not exclusively, due to excessive activity of specific cAMP-phosphodiesterases. The abnormality can be overcome in vitro and in vivo by the phosphodiesterase inhibitor, rolipram. Most cases of hereditary NDI in man have sex-linked recessive inheritance, which appears to be due to an abnormality of the V2 receptor. The chromosomal locus of the defect is Xq28. Sporadic cases of congenital NDI have been described in females who appear to have a defect beyond the V2 receptor and the guanine nucleotide-binding stimulatory protein. There is no information on the biochemical defect in very rare cases with other types of inheritance patterns. No abnormalities of V1a and V1b receptor function have been found in patients with NDI. Mice and patients with NDI have evidence of increased AVP synthesis. AVP release in relation to plasma osmolality is increased in patients during infusion of hypertonic saline. This is the opposite of what has been described in patients with primary polydipsia (dipsogenic diabetes insipidus) who are chronically overhydrated. Together, these studies indicate that chronic dehydration and overhydration can cause up- and downregulation of the osmotic release of AVP.

Congenital Short Gut, Malrotation, and Dysmotility of the Small Bowel

A familial syndrome of congenital short small bowel, malrotation, and functional bowel obstruction is presented and illustrated in three male siblings with one long-term survivor. Including the present three cases there have been 18 similar cases found in the literature. This disorder appears to be a sex-linked recessive inheritance. Early barium meal and follow through in siblings of patients with this condition will detect malrotation that should be surgically corrected in order to prevent mid-gut volvulus. Intravenous alimentation and early introduction of enteral feeding is important, not only to maintain nutrition but to encourage adaptation of the associated short and dysmotile bowel. These measures aim to improve the outcome of this frequently, but not invariably, fatal disorder.

Síndrome de Menkes: revisão da patogenia a propósito de um caso anatomo clínico

É relatado um caso de síndrome de Menkes, que acreditamos ser o primeiro descrito no Brasil. O paciente, menino de 15 meses, apresentava, desde o quinto mês de vida, pili torti, grave involução do desenvolvimento neuropsicomotor e síndrome convulsiva. Os exames complementares evidenciaram ceruloplasmina e cobre séricos baixos, alterações arteriais e intensa atrofia cerebral difusa. O exame necroscópico confirmou este último aspecto, observando-se despopulação neuronal nas camadas mediocorticais do cérebro, no tálamo e sobretudo no cerebelo, sede de lesões intensas e particulares em nível cortical. Acredita-se que a síndrome de Menkes, de herança recessiva ligada ao sexo, seja devida a um erro inato do metabolismo do cobre, primário ou secundário a alterações variáveis das proteínas que permitem o transporte de cobre aos diferentes tecidos. Os autores revisam os principais aspectos etiopatogênicos referidos na literatura.

えん下障害を主訴とした球せき髄性筋い縮症の１家系

Bulbar spinal muscular atrophy is very rare disease. The disease is characterized by clinical onset in adult, slowly progressive course, sex-linked recessive inheritance, signs of bulbar palsy, generalized fasciculation and absence of pyramidal tract lesion.This paper describes a family in which 6 members, all male, were affected by the disease. In our cases, clinical onset was fifth and sixth decades and bulbar palsy appeared in four cases and muscular weakness came out in proximal muscles initially. We summarized the clinical features and the prognosis of this disease through a survey of the literatures. Moreover, we investigated a cause of dysphagia of the present cases by the measurement of the pharyngoesophageal intraluminal pressure and esophagogram. As a result of the measurement, it was revealed that the pharyngeal phase of deglutition was disturbed.

A hemophiliac dog colony: Genetic studies and coagulation findings in hemophiliac and normal dogs

1. 1. A colony of hemophiliac dogs was developed as descendants of a single affected Pomeranian. Over a 13 year period, a total of 29 hemophiliac dogs survived to the age of 6 months or longer. Eleven were female and 18 were male. All five of the possible matings in a sex-linked recessive inheritance pattern were accomplished and the offspring fell into the expected sex and disease groups. 2. 2. Twenty-one dogs died from untreated hemorrhages which usually occurred in loose tissues or body cavities during the night. Clinically, there were no hemarthroses but 22 other hemorrhages responded promptly to treatment with dog cryoprecipitate. 3. 3. Coagulation studies showed that the hemophiliac dogs averaged about 0.23 U/ml equivalents of human F VIII:C while normal dogs averaged 8.0 U/ml equivalents of human. F's V, VII, II, X, IX, XI and XII were higher than human in both normal and hemophiliac dogs. Dog fibrinogen fell within the human range and Fletcher F was very low.

The prognostic value of presenting serum LDH in non-Hodgkinlymphoma

The parents of the propositi had normal circulating calcium and inorganic phosphate values. X-linked recessive inheritance of IHP seemed well established, although none of the affected male subjects had children so thai mate-to-male transmission could be excluded or their daughters could be shown to be carriers. Peden suggested that sex-linked transmission might be the most common pattern of inheritance tbr IHP presenting in infancy. Our findings support Peden's conclusions. X-linked recessive inheritance seems certain for IHP in the kindred reported herein. Although we too did not have the opportunity to observe absence of male-to-male transmission or an obligate carrier state for IHP in the daughters of affected men to support sex-linked inheritance, IHP was confirmed in male members of three generations and almost certainly affected infant boys in four generations. There was no history of seizures or other problems to suggest IHP in female family members. Normal circulating calcium, inorganic phosphate, and immunoreactive parathyroid hormone values in the propositi's mother further supported sex-linked recessive inheritance; her unremarkable biochemical values and normal X chromosome morphology suggest that carriers cannot be readily identified. Provocative tests, however, such as ethylenediamine tetraacetic acid infusion, 4 were not used to study parathyroid hormone reserve. Although it is remarkable that both reports of X-linked recessive IHP should come from St. Louis, we could find no evidence that we and Peden had studied the same kindred. The nosology Of hypoparathyroidi sm is complex and incomplete?. 2. s In addition to a variety of problems characterized by transient hypoparathyroidi sm, persistent IHP can occur in infancy. Although most cases of IHP reported in infancy are sporadic, some are inherited; both autosomal dominant 6 and X-linked recessive 3 patterns occur. Pediatricians must be aware of this familial nature of IHP since screening of new or old family members could uncover a disorder with serious consequences if untreated.

Motoneuropathie héréditaire: La forme proximale de l'adulte liéé au sexe (ou maladie de kennedy): Observations cliniques et neuroendocrinologiques

Clinical, electrophysiological, histological and neuroendocrinological findings in a peculiar form of progressive spinal and bulbar muscular atrophy affecting 4 members in two different families are reported. The clinical hallmarks, which characterize this entity among the group of degenerative motor neuron diseases are: sex-linked recessive inheritance; onset in the third decade; slow progression; involvement of facial and bulbar muscles in addition to wasting of the proximal and, in some cases, the distal musculature; asymmetry of clinical signs; consistent and abundant fasciculations predominantly in the peri-oral muscles; intention tremor and a well-developed gynaecomastia, which is the first clinical sign. Electrophysiological and histological findings confirm the neurogenic origin of the muscular atrophy; in addition, muscle biopsy shows “myopathic-like” changes in one case and serum muscle enzyme levels are elevated in all neurologically affected patients. It is believed that the clinical entity corresponds to the rare type III proximal hereditary motor neuropathy (or “Kennedy's disease”), of which 25 published cases are reviewed. Neuroendocrinological data in two patients demonstrate an androgenic insufficiency of hypothalamo-hypophyseal origin and high levels of circulating oestrogens, which probably have induced gynaecomastia. Dynamic neuroendocrinological tests suggest that lesions of certain hypothalamic nuclei may exist, which should be looked for in forthcoming anatomical studies.

Calculating genetic risk figures using a programmable pocket calculator.

In autosomal irregular dominant as well as in sex-linked recessive inheritance, heterozygosity probabilities for up to six or eight pedigree members with unknown genotype can easily be calculated using a programmable pocket calculator. The application of the underlying combinatorial programs is explained by means of two relevant examples. Genetic counsellors without a computer at hand are provided with a simple and accurate method for calculating genetic risk figures taking into account pedigree data, incidence and/or mutation rate, reproductive fitness, as well as penetrance or results of heterozygosity tests of the disease in question.

X-linked spinal and bulbar muscular atrophy of late onset: A separate type of motor neuron disease?

The clinical, electrophysiological and muscle biopsy findings of 7 cases with a peculiar form of X-linked hereditary degenerative motor neuron disease are presented. It is suggested that the disease might be a separate clinical entity with the following characteristics: (1) sex-linked recessive inheritance, (2) unusual but not invariable late onset, (3) slow progression, (4) facial-bulbar and proximal spinal muscle involvement, (5) consistent fasciculations, sometimes massive and more pronounced about the lips, chin and tongue, (6) fine tremor of the hands, (7) muscle cramps usually preceding the other symptoms, and (8) gynaecomastia as a frequent but not a constant feature.

X-LINKED RECESSIVE PROGRESSIVE COMBINED VARIABLE IMMUNODEFICIENCY (DUNCAN'S DISEASE)

Of 18 boys in the Duncan kindred, 6 died of a lymphoproliferative disease. They exhibited a subtle, progressive combined variable immunodeficiency disease characterised by benign or malignant proliferation of lymphocytes, histiocytosis, and alterations in concentrations of serum-immunoglobulins. Infectious mononucleosis occurred during or preceding terminal events in at least 3 of the cousins. Fever, pharyngitis, lymphadenomegaly, hepatosplenomegaly, atypical lymphocytosis, and a spectrum ranging from agammaglobulinæmia to polyclonal hypergammaglobulinæmia occurred. At necropsy, the thymus glands and thymic-dependent areas in the lymph-nodes and spleen were depleted of lymphocytes. Diffuse infiltrates composed of lymphocytes, plasma cells, and histiocytes, some containing erythrocytes, invaded the hæmatopoietic organs, viscera, and central nervous system. In addition, 2 half-brothers had lymphomas of the ileum and central nervous system. Approximately half the boys, including the half-brothers, were affected, and girls were spared, implying sex-linked recessive inheritance. Various lymphohistiocytoses resemble Duncan's disease, but it is distinctive from them in the mode of inheritance or by histological characteristics. This study suggests that the Epstein-Barr virus or other viruses triggered the fatal proliferation of lymphocytes and that progressive attrition of T-cell function allowed uncontrolled lymphoproliferation.

Fatty acid oxidation by skeletal muscle mithochondria in duchenne dystrophy

In a study of palmitate oxidation by skeletal muscle mitochondria in Duchenne muscular dystrophy, it was found that in cases with a family history of sex-linked recessive inheritance palmitate oxidation was markedly reduced whereas in isolated cases the values were essentially normal. Reduced values of palmitate oxidation were also observed in the definite female carriers o the sex-linked dystrophic gene. These findings suggest that isolated cases may have a different disorder from the cases of familial Duchenne muscular dytrophy.