Compound Heterozygote Mutations Research Articles

Annual change in eGFR in renal hypouricemia: a retrospective pilot study.

Extremely low uric acid (UA) levels or increased urinary UA (Uua) excretion might be risk factors for kidney disease in renal hypouricemia (RHU) patients, but their relationship with kidney dysfunction is unclear. This study investigated time-dependent changes in eGFR in RHU patients. This multicenter retrospective study assessed UA metabolism and changes in eGFR (median 5.5years) in 13 RHU patients. We then compared eGFR change in 7 of 13 RHU patients whose eGFR could be measured for 4years with those in normouricemic group (n = 31). In addition, 7 RHU patients were divided into two groups based on URAT1 gene mutations: homozygote and compound heterozygote mutations (Homo/Com group, n = 3), and wild-type and heterogeneous mutations (WT/Hetero group, n = 4). In 13 RHU patients, the median and mean serum UA (SUA) were 0.8 (0.4-2.5) and 1.1 ± 0.7mg/dL. The median and mean Uua were 44.3 (12.7-141.1) and 49.7 ± 36.2mg/dL. The median and mean urinary urate clearance (Cua/Ccr) were 46.8 (11.3-73.6) and 43.3 ± 19.7%. Over 4years, eGFR did not change in the RHU group but declined in the normouricemic group. Annual mean eGFR decline and change rate in the RHU group were the same as those in the normouricemic group (- 1.09 ± 1.11 vs. - 1.09 ± 1.92mL/min/1.73 m2/year, p = 0.996) (- 1.74 ± 1.96 vs. - 1.36 ± 2.10%, p = 0.664). And no significant difference was found in eGFR decline or change rate between Homo/Com and WT/Hetero groups (- 0.33 ± 1.03 vs. - 1.67 ± 0.85mL/min/1.73 m2/year, p = 0.116) (- 0.61 ± 1.62 vs. - 2.59 ± 1.91%, p = 0.210). RHU from URAT1 genetic mutation may not show eGFR decline over 4 consecutive years.

Establishment of human induced pluripotent stem cell line SDQLCHi029-A from one Type 1 familial glucocorticoid deficiency patient carrying compound heterozygote mutations in MC2R gene

Type 1 familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder due to variation of the melanocortin-2-receptor (MC2R) gene. Induced pluripotent stem cell (iPSC) line SDQLCHi029-A was successfully generated from peripheral blood mononuclear cells obtained from a 5-day-old girl with MC2R mutations (c.428C > T and c.409C > T). The iPSC line showed genetically stable and matched the donor’s PBMCs. displayed a normal karyotype, expressed high pluripotent markers, and exhibited differentiation potential of three germ layers in vitro. The iPSC line could be a good model to study the pathogenesis of FGD type 1 and screen new drugs for the disease.

Novel OBSL1 Variant in a Chinese Patient with 3M Syndrome and the c.458dupG Mutation May Be a Potential Hotspot Mutation in the Chinese Population.

3M syndrome is an autosomal recessive disorder characterized by short stature and skeletal developmental abnormalities. In this study, a Chinese patient with 3M syndrome was presented. A novel OBSL1 (obscurin-like 1 gene) variant was found. The patient is a 2-year-old girl who presented with short stature and had intrauterine growth retardation and low birth weight. Gene analysis revealed compound heterozygote mutations in the OBSL1 gene: c.458dupG (p.L154Pfs*100) and c.427dupG (p.A143Gfs*111). The c.427dupG mutation is novel. The c.458dupG mutation has been documented in 5 cases, occurring only in Chinese individuals, indicating ethnic specificity. In cases of short-statured children presenting intrauterine growth retardation, low birth weight, and skeletal developmental abnormalities, 3M syndrome should be considered. The c.458dupG mutation might be a hotspot mutation in the Chinese population.

Establishment of a non-integrated iPSC line (SDQLCHi043-A) from a male infant with propionic acidemia carrying compound heterozygote mutations in PCCB gene

In this study, peripheral blood mononuclear cells were contributed from a male infant with propionic acidemia (PA) verified by clinical and genetic diagnosis, who inherited compound heterozygous mutations in the propionyl-CoA carboxylase subunit beta (PCCB) gene. Here, this iPS was generated by non-integrated episomal vectors with SOX2, BCL-XL, OCT4, C-MYC and OCT4. Also, this iPSC line exhibited the morphology of pluripotent stem cells, upward mRNA and protein expression of pluripotency markers, conspicuous in vitro differentiation potency and regular karyotype, and carried PCCB gene mutations, which provided an excellent model for the research and drug screening of PA.

Early versus late diagnosis of LAMA2 congenital muscular dystrophy: a distinct consequence

BackgroundLaminin subunit alpha 2 (LAMA2)-related muscular dystrophy (LAMA2 MD) is caused by homozygous or compound heterozygous mutations in LAMA2 (OMIM#156225), located on chromosome 6q22.Case presentationWe describe two patients with LAMA2 MD treated at a Taiwanese hospital. Both presented with gradual hypotonia starting in early infancy. A targeted muscular dystrophy/myopathy panel and whole-exome sequencing were used as diagnostic tools in both patients. In Patient 1, a maternally inherited variant (NM_000426.3:c.7525_7528dupCTCA/ p.Ser2510ThrfsTer3) and a paternally inherited variant (c.112 + 2 T > C) were revealed. In Patient 2, compound heterozygote mutations in LAMA2 were identified: 1) c.1583dupA(p.S529Efs*18) in exon 11, inherited paternally, and 2) c.A6931T:p.K2311X in exon 49, inherited maternally. The discovery of these four mutations enriches the genetic spectrum of LAMA2 MD.ConclusionsWe suggest that comprehensive genetic investigations be performed as early as possible in patients with suspected muscular dystrophy to provide appropriate treatment.

A New Case of Abetalipoproteinemia Caused by Novel Compound Heterozygote Mutations in the MTTP Gene without Fat or Vitamin Malabsorption.

Abetalipoproteinemia (ABL) is a rare disease characterized by extremely low apolipoprotein B (apoB)-containing lipoprotein levels, dietary fat, and fat-soluble vitamin malabsorption, leading to gastrointestinal, neuromuscular, and ophthalmological symptoms. We herein report a case of ABL with novel compound heterozygous mutations in the microsomal triglyceride transfer protein gene (c.1686_1687del [p.Ser563TyrfsTer10] and c.1862T>C [p.Ile621Thr]), identified via panel sequencing. Although the patient had extremely reduced low-density lipoprotein cholesterol levels and a fatty liver, he did not exhibit other typical complications. Furthermore, unlike typical ABL, this patient had a preserved apoB-48 secretion and increased concentrations of high-density lipoprotein cholesterol, which may account for the normal serum fat-soluble vitamin levels.

Cryopyrin-associated periodic fever syndrome (CAPS) presenting as early-onset dementia, lacking typical recurrent fever or skin rash: a case report

A 54-year-old man with a university degree was admitted to our hospital because of a two-year history of progressive dementia. He had familial sensorineural hearing loss and had been treated for epilepsy since his 30s. On admission, he showed severe dementia and parkinsonism without fever or skin rash. Systemic inflammation was evident, and the CSF cell count and IL-6 level were elevated to 53/μl and 307 ‍pg/ml, respectively. Brain MRI demonstrated diffuse brain atrophy. More detailed anamnesis revealed a history of rheumatoid arthritis in childhood and aseptic meningitis in his 20s. Genetic examination for autoinflammatory diseases demonstrated compound heterozygotic mutations in the NLRP3 gene, causing cryopyrin-associated periodic fever syndrome (CAPS). This case was atypical CAPS presenting as early-onset progressive dementia, without recurrent fever or urticaria-like eruption which are usually seen in this disease.

An interleukin 10 Receptor alpha (IL-10RA) variant with a compound heterozygote mutation shows normal IL-10 signaling activity

An interleukin 10 Receptor alpha (IL-10RA) variant with a compound heterozygote mutation shows normal IL-10 signaling activity

Effect of Rosa canina Methanol Extract on Membrane Trafficking in Different Niemann‐Pick C1 Phenotypes

Niemann Pick type C (NPC) disease is an autosomal recessive lysosomal storage disorder that is caused by mutations in Niemann‐Pick C1 (NPC1) or Niemann‐Pick C2 (NPC2) genes ultimately leading to progressive neurological deterioration. 95% of NPC cases arise from mutations in the NPC1 gene. NPC1 protein mediates the intracellular cholesterol trafficking and plays a crucial role in maintaining lipid homeostasis. Mutations in NPC1 are associated with defective cholesterol mobilization and an accumulation of unesterified cholesterol and subsequently sphingomyelin and glycosphingolipids in the late endo‐lysosomes. N‐butyldeoxynojirimycin, known as Miglustat, is one of the approved therapeutic options. It is an inhibitor of sphingolipid synthesis and is used in substrate reduction therapy. Nevertheless, the efficiency of Miglustat varies among NPC patients depending on the type of the mutation and moreover its accompanied by several side effects, such as diarrhea. The focus of this study is to find an alternative therapy that presents less side effects. Rosa canina L. methanol extract (RCME) has been shown to improve the protein trafficking and maintain cholesterol homeostasis. Here, we used skin‐derived fibroblasts from patients harbouring homozygote or compound heterozygote mutations to assess the effects of RCME on the trafficking of NPC1 and cellular cholesterol contents as compared to wild type cells. For this purpose, the cells were treated for 24 h with RCME (100 µg/ml) with and without Miglustat (100 µM) and the trafficking of NPC1 between the endoplasmic reticulum (ER) and the Golgi was examined by endoglycosidase H treatment. This treatment, which discriminates between mannose‐rich N‐linked glycosylated proteins and mature complex glycosylated forms, demonstrated a significant enhancement of the trafficking of a NPC1 mutants between the ER and the Golgi upon RCME treatment as compared to Miglustat. This trafficking behaviour was observed with those NPC1 mutants that are not entirely blocked in the ER and exit the ER at a slow rate. Markedly, the high cholesterol levels measured in the patients’ fibroblasts are substantially reduced upon RCME treatment, while almost similar cholesterol levels were maintained in the wild type cells. Impaired cellular cholesterol trafficking is associated with partial distortion of the lipid membrane composition, particularly of the cholesterol‐ and sphingolipids‐enriched membrane microdomains or lipid rafts (LRs). Our data show that RCME and also Miglustat maintained a normal LRs distribution as assessed by the LR marker flotillin 2.We conclude that RCME possess the capacity to reverse adverse effects caused by mutations in the NPC1gene including impaired NPC1 trafficking, elevated cholesterol levels and lipid raft alterations. All this together render the constituents of RCME, including quercetin, a promising agents in NPC therapy.

Clinical, laboratory data and outcomes of 17 Iranian citrullinemia type 1 patients: Identification of five novel ASS1 gene mutations.

Citrullinemia type 1 is an autosomal recessive metabolic disease caused by ASS1 gene mutations encoding argininosuccinic acid synthetase enzyme which is within the pathway of arginine and nitric oxide biosynthesis. Disease confirmation was done by ASS1 gene mutation analysis using next‐generation sequencing, DNA Sanger sequencing. The study group was 17 citrullinemia type 1 patients from 10 unrelated families referred to Iranian National Society for Study on Inborn Errors of Metabolism's clinic between 2008 and 2020. Clinical, laboratory, and molecular data were retrospectively evaluated. Eleven different ASS1 gene mutations were detected in 13 (76%) of 17 neonatal, three (18%) of 17 late infantile, and one (6%) of 17 asymptomatic patients. Severe developmental delay and intractable seizures despite metabolic control was outcome of neonatal form survivor. Two late infantile form patients live metabolically controlled with quite normal performance. DNA mutations are as follows: seven missense, one nonsense, and two insertion/deletion mutations in 12, two, and three patients, respectively. Five novel mutations were detected including a homozygous GG deletion in exon 12 (c.790_791delGG;p.Gly264Profs*3) and a homozygous mutation in exon 7 (c.440C>T; p.Met147Thr), both causing infantile (late onset) form; a homozygous mutation in exon 6 (c.1130T>C; p.Met376Thr) causing neonatal form; two compound heterozygote mutations in exon 14 (c.1167_1168insC:p.Gly390Argfs*22& c.1186T>A; p.Ser396Thr) causing asymptomatic form. Five (38%) patients with classic neonatal form had mutation in exon 14 of ASS1 (c.1168G>A; p.Gly390Arg). Classic neonatal was the most common form of disease in Iranian‐studied patients and homozygote c.1168G>A was the most frequent ASS1 gene mutation. Global neonatal screening for citrullinemia type 1 in Iran is recommended and certain mutations can be used for screening severe form in this population.

Congenital Metabolic Bone Disorders as a Cause of Bone Fragility.

Bone fragility is a pathological condition caused by altered homeostasis of the mineralized bone mass with deterioration of the microarchitecture of the bone tissue, which results in a reduction of bone strength and an increased risk of fracture, even in the absence of high-impact trauma. The most common cause of bone fragility is primary osteoporosis in the elderly. However, bone fragility can manifest at any age, within the context of a wide spectrum of congenital rare bone metabolic diseases in which the inherited genetic defect alters correct bone modeling and remodeling at different points and aspects of bone synthesis and/or bone resorption, leading to defective bone tissue highly prone to long bone bowing, stress fractures and pseudofractures, and/or fragility fractures. To date, over 100 different Mendelian-inherited metabolic bone disorders have been identified and included in the OMIM database, associated with germinal heterozygote, compound heterozygote, or homozygote mutations, affecting over 80 different genes involved in the regulation of bone and mineral metabolism. This manuscript reviews clinical bone phenotypes, and the associated bone fragility in rare congenital metabolic bone disorders, following a disease taxonomic classification based on deranged bone metabolic activity.

Clinical significance of MEFV gene variation R202Q.

The aim of this study was to evaluate the phenotypic features and the clinical significance of the R202Q mutation of the MEFV gene. We retrospectively reviewed the medical records of Familial Mediterranean Fever patients with M694V/- and M694V/R202Q mutations. We compared the patients regarding disease severity, symptoms, age at the onset of symptoms, gender, consanguinity, and family history. Twenty-one patients (9 males, 12 females) had compound heterozygote mutation (M694V/R202Q), and 37 patients (23 males, 14 females) had M694V/- mutation. The mean age of the patients at the time of diagnosis was 7.3 ± 4.3 and 9.2 ± 3.7years. The rate of arthritis was significantly higher in patients with M694V/R202Q heterozygote mutation than those with M694V/- heterozygote mutation (76.2% vs 32.4%; p = < 0.001). The mean severity score was higher in M694V/R202Q heterozygote group although it did not reach statistical significance (8.43 ± 1.69 vs 7.49 ± 1.50; p = 0.082). However, the rate of having a high severity score was significantly higher in the M694V/R202Q mutation group than in the other group (47.6% vs 21.6%, respectively; p = 0.039). The rate of arthritis was significantly higher in patients with M694V/R202Q heterozygote mutation than those with M694V/- heterozygote mutation (76.2% vs 32.4%; p = < 0.001). Our finding supports the possibility that R202Q may be pathogenic rather than a variation. We found that the R202Q mutation is associated with the inflammatory phenotype of FMF; hence, the typical clinical findings of FMF especially arthritis can be observed in patients with compound mutation including R202Q. Key Points • We found that the R202Q mutation is associated with the inflammatory phenotype of FMF • The patients with the R202Q mutation had a greater rate of arthritis symptoms.

Compound Heterozygous Myosin 5B (Myo5b) Mutation with Early Onset Progressive Cholestasis and No Intestinal Failure

Background Exome sequencing studies have recently identified novel genes implicated in normal or low GGT pediatric cholestasis including myosin 5B (MYO5B). Case report: We identified novel compound heterozygote mutations in exon 14 and exon 19 of the MYO5B gene in an 18-month-old Indian child with history of fluctuating jaundice and severe pruritus. His liver biopsy showed portal and perivenular fibrosis with focal bridging septa and mild activity. He is currently on UDCA, cholestyramine and vitamin supplements. There is no history of diarrhea. His asymptomatic mother showed heterozygous mutation in exon 19 of the MYO5B gene and his asymptomatic father showed heterozygous mutation in exon 14 of the MYO5B gene. Conclusion: Our report confirms that patients with compound heterozygote mutations in MYO5B develop progressive cholestasis with no intestinal disease.

Abrogated GADD45b-Mediated Integrity Control of Hematopoietic Stem Cells upon ER Stress and DNA Damage Triggers Lymphopoiesis over Granulopoiesis in Congenital Neutropenia

In patients with severe congenital neutropenia (CN) with maturation arrest of bone marrow granulopoiesis, hematopoietic and myeloid progenitor cells exhibit elevated endoplasmic reticulum (ER) stress and unfolded protein response (UPR) due to inherited mutations in ELANE (neutrophil elastase, NE) or HAX1 (HCLS1-associated protein X-1). UPR and ER stress may induce genetic instability in hematopoietic stem and progenitor cells (HSPCs). Indeed, we recently reported severe changes in cell cycle control and DNA repair pathways (e.g. CHEK1 and BRCA1) in HSPCs of CN patients, as compared to G-CSF treated healthy individuals. We further studied the molecular mechanism of the hyper-sensitivity of CN HSPC to stress conditions. We found that expression of Growth Arrest and DNA-Damage-inducible, beta (GADD45b), which functions as stress sensor regulating cell cycle, survival and apoptosis in response to ER stress or DNA damage, was markedly reduced in myeloid progenitors of CN patients, as compared to G-CSF-treated healthy individuals. GADD45b is essential in stress-induced murine hematopoiesis and myeloid differentiation is severely compromised in gadd45b knockout mice (Gupta S. et al., 2006). Less is known about the functions of GADD45b in the DNA damage response and myeloid differentiation of human HSPCs. To study GADD45b functions in human hematopoiesis, we generated human induced pluripotent stem cells (iPSC) of healthy individuals haplo-insufficient for GADD45b using CRISPR/Cas9-mediated knockout of GADD45b . Human iPSCs were transfected with GADD45b -specific CRISPR/Cas9-gRNA RNP and gene-edited clones were selected for further study. We could not detect any iPSCs clones with frameshift homozygote or compound heterozygote mutations in exon 1 of GADD45b leading to the complete knockout of GADD45b . Most probably GADD45b-deficient iPSCs are lethal. GADD45b+/- iPSCs also presented a profound phenotype. While these cells retained pluripotency, we detected elevated γH2AX levels in GADD45b+/- iPSCs upon UV light exposure, as compared to GADD45b-WT cells. In line with up-regulated γH2AX levels, we measured strongly induced DNA damage, as quantified by Lord-Q DNA damage assay. We further analyzed myeloid differentiation of GADD45b+/- iPSCs using embryoid body (EB)-based method and found that GADD45b+/- iPSCs cells completely lost the capacity to differentiate into hematopoietic cells. We were able to make EBs of GADD45b+/- cells, these EBs survived and showed no signs of degradation or cell death, but they produced no floating (hematopoietic) cells. To study the effects of GADD45b inhibition in hematopoietic cells we transfected bone marrow CD34+ cells with GADD45b -specific CRISPR/Cas9-gRNA RNP. Similar to iPSCs, we detected markedly elevated UV-induced DNA damage and diminished G-CSF-mediated myeloid differentiation of GADD45b-edited CD34+cells in colony-forming units (CFU) assay. These data strongly support the essential role of GADD45b in hematopoietic and myeloid differentiation. Diminished GADD45b expression in CN HSPCs may increase susceptibility to stress and may contribute to malignant transformation.In order to prevent the appearance and clonal outgrowth of stressed HSPCs with inherited disease-causing mutations in combination with acquired oncogenic mutations, intrinsic DNA damage must be tightly controlled. Failures in the control mechanisms may affect the fate of HSPCs as for instance altered proliferation and wrongly biased differentiation. Therefore, we further evaluated the composition of the HSPC pool in GADD45b-deficient bone marrow cells of CN patients (CN- ELANE n=5, CN- HAX1 n=5), in comparison to healthy individuals treated (n=5) or not (n =7) with G-CSF using multicolor FACS panel of J. Dick. Treatment of healthy individuals with G-CSF induces increase of common myeloid progenitors (CMP, 7-fold) and decrease of multi-lymphoid progenitors (MLP, 10-fold). At the same time, the hematopoietic differentiation in CN patients is substantially shifted from CMP (14-fold decrease) to MLP (36-fold increase) lineage with dramatically reduced numbers of GMPs (3-fold) and increased numbers of B/NK progenitors (5-fold). These data suggest that deregulated integrity control of HSPC pool due to elevated UPR and ER stress and reduced GADD45b expression in hematopoietic cells of CN patients may change composition of HSPC pool and G-CSF response. DisclosuresNo relevant conflicts of interest to declare.

An induced pluripotent stem cell line (NCATS-CL9075) from a patient carrying compound heterozygote mutations, p.R390P and p.L318P, in the NGLY1 gene

NGLY1 deficiency is a rare disorder caused by mutations in the NGLY1 gene which codes for the highly conserved N-glycanase1 (NGLY1). This enzyme functions in cytosolic deglycosylation of N- linked glycoproteins. An induced pluripotent stem cell (iPSC) line was generated from the dermal fibroblasts of a 2-year-old patient carrying compound heterozygous mutations, p.R390P and p.L318P in the NGLY1 gene. This cell-based iPSC disease model provides a resource to study disease pathophysiology and to develop a cell-based disease model for drug development for NGLY1 patients.

Generation of an induced pluripotent stem cell line SDQLCHi026-A from a hereditary tyrosinemia type I patient carrying compound heterozygote mutations in FAH gene

Here we describe the generation of induced pluripotent stem cells (iPSCs) from a patient diagnosed as hereditary tyrosinemia type I (HT1) caused by FAH gene mutation. Induced pluripotent stem cells (iPSCs) were developed using non-integrating episomal vectors containing OCT4, SOX2, KLF4, BCL-XL and MYC. The established iPSC line (SDQLCHi026-A) displayed pluripotent cell morphology, high expression levels of pluripotency markers, differentiation potential in vitro, normal karyotype, and remaining the original FAH gene mutation.

Osteoarticular manifestations as initial symptoms of WD with novel compound heterozygote mutations in the ATP7B gene: a case report

Wilson disease (WD) is a rare autosomal recessive disease characterized by hepatic, neurologic and psychiatric, and variable manifestations. Skeletal and articular manifestations are usually overlooked at an early stage in WD patients, which have an effect on therapeutic outcome and prognosis. We report a 13-year-old girl of Chinese Han ethnicity with arthralgia and fracture as initial symptoms of WD. Laboratory tests showed her 1:80 of antinuclear antibodies (ANA). The patient was diagnosed with oligoarticular juvenile idiopathic arthritis (JIA) and treated with 10 mg of methotrexate (MTX) every week and diclofenac sodium every day. Her symptoms showed no improvement over 6 months and her medications were ceased. Then the patient presented to our department with a 3-week history dysarthria, gait abnormalities, dystonia and tremor. Kayser-Fleischer rings, serum ceruloplasmin and liver biopsy confirmed the diagnosis of WD. Genetic analysis was performed using SureSelect Clinical Research Exome v2 and then verified by bi-directional Sanger sequencing. We found that the patient carried a novel compound heterozygous mutation in ATPase copper transporting beta (ATP7B) on both chromosomes, which consist of a heterozygote of NM_000053.3 (ATP7B): c.3884C>T p. Ala1295Val and large fragment heterozygous deletion in exons 10–11 of ATP7B gene identified using multiplex ligation-dependent probe amplification (MLPA), to be inherited from her asymptomatic parents, respectively. The patient’s symptoms were relieved at the 1-year follow-up after treatment with D-penicillamine and oral zinc. This case highlights that WD should be taken into consideration in adolescents with unexplained joint pain, arthritis, and fracture of the large joints.

Novel mechanism of hereditary pyropoikilocytosis phenotype due to co‐inheritance of β globin and α spectrin mutations

Novel mechanism of hereditary pyropoikilocytosis phenotype due to co‐inheritance of β globin and α spectrin mutations

Pompe Disease Screening in a Sample of Iranian Patients

The reason why the experiments were done: previous studies have shown that the incidence rates vary in different populations. Now we report the preliminary results of the screening study. Pompe disease is a rare but potentially treatable disorder caused by the deficiency of the lysosomal enzyme acid-α-glucosidase (GAA). GAA activity was measured on DBS in 65 patients with undiagnosed myopathies presenting to the hospital of the research setting in Isfahan, Iran, from 2016 to 2017 and then was confirmed by genetic analysis. Of the total of 65 patients, 29 (44.6%) were male, and 36 (55.4%) were female. The mean age of the patients was 29±12.55 years, and their mean age at the disease onset was 17±12.75. Two patients (one male and one female) were diagnosed with a low acid alpha-glucosidase activity. Only one patient (female) showed a compound heterozygotic mutation of the GAA gene (c.-32-13T&gt;G). Early diagnosis of Pompe disease is important for improving the outcome.

Generation and characterization of an integration-free iPSC line SDUBMSi006-A from a patient with Alport syndrome caused by COL4A3 gene mutations.

Alport syndrome (AS) is a hereditary kidney disease caused by mutations in COL4A3, COL4A4, or COL4A5 genes. Here we report the generation of an induced pluripotent stem cell line (iPSC) from an AS patient carrying compound heterozygote mutations (c.4243G>C and c.4216G>A) in COL4A3 gene using non-integrative reprogramming technology. The established iPSC line demonstrates hESC morphology, expresses pluripotency markers, has normal karyotype, and is capable of differentiating into all three germ layers in vitro.