-
1.
A novel compound heterozygous mutation in SLC5A2 contributes to familial renal glucosuria in a Chinese family, and a review of the relevant literature.
Li, S, Yang, Y, Huang, L, Kong, M, Yang, Z
Molecular medicine reports. 2019;(5):4364-4376
-
-
Free full text
-
Abstract
Familial renal glucosuria (FRG) is a rare condition that involves isolated glucosuria despite normal blood glucose levels. Mutations in the solute carrier family 5 member 2 (SLC5A2) gene, which encodes sodium‑glucose cotransporter 2 (SGLT2), have been reported to be responsible for the disease. Genetic testing of the SLC5A2 gene was conducted in a Chinese family with FRG. A number of online tools were used to predict the potential effect of the identified mutations on SGLT2 function. Additionally, the SLC5A2 mutations previously reported in PubMed were summarized. A novel compound heterozygous mutation (c.514T>C, p.W172R; c.1540C>T, p.P514S) of the SLC5A2 gene in a Chinese child with FRG was identified. In total, 86 mutations of the SLC5A2 gene have been reported to be associated with FRG. The novel compound heterozygous mutation (c.514T>C, p.W172R; c.1540C>T, p.P514S) of the SLC5A2 gene may be responsible for the onset of FRG. The present study provides a starting point for further investigation of the molecular pathogenesis of the SLC5A2 gene mutation in patients with FRG.
-
2.
A novel PHKA2 mutation in a Chinese child with glycogen storage disease type IXa: a case report and literature review.
Fu, J, Wang, T, Xiao, X
BMC medical genetics. 2019;(1):56
Abstract
BACKGROUND PHKA2 gene mutations can cause liver phosphorylase kinase (PhK) deficiency, resulting in glycogen storage disease type IXa (GSD IXa). Elevated liver transaminase levels and liver enlargement are the most frequent phenotypes of GSD IXa. However, whether the phenotypes are applicable to Chinese patients remains unclear. CASE REPORT A boy aged 2 years and 8 months with a history of episodic fatigue and weakness since he was 2 years old was referred to our endocrinology clinic. Apart from symptomatic ketotic hypoglycemic episodes (palpitation, hand shaking, sweating, etc.), no abnormalities of liver transaminase levels or liver size were found. To identify the aetiology of his clinically diagnosed hypoglycaemia, the proband and his parents were screened for PHKA2 gene mutations by next-generation sequencing. A heterozygous mutation (c.2972C > G, p.G991A) in PHKA2 was found in the proband and his mother. Twenty-one Chinese cases with GSD IXa have been reported in the literature to date, and elevated liver transaminase levels (95%) and liver enlargement (91%) are the most frequent phenotypes of GSD IXa in Chinese patients. Hypoglycaemia may be one of the early onset symptoms in infants with GSD IXa. CONCLUSIONS This study enriches our knowledge of the PHKA2 gene mutation spectrum and provides further information about the phenotypic characteristics of Chinese GSD IXa patients.
-
3.
Long-term follow-up in a Chinese child with congenital lipoid adrenal hyperplasia due to a StAR gene mutation.
Zhao, X, Su, Z, Liu, X, Song, J, Gan, Y, Wen, P, Li, S, Wang, L, Pan, L
BMC endocrine disorders. 2018;(1):78
Abstract
BACKGROUND Congenital lipoid adrenal hyperplasia (CLAH) is an extremely rare and the most severe form of congenital adrenal hyperplasia. Typical features include disorder of sex development, early-onset adrenal crisis and enlarged adrenal glands with fatty accumulation. CASE PRESENTATION We report a case of CLAH caused by mutations in the steroidogenic acute regulatory protein (StAR) gene. The patient had typical early-onset adrenal crisis at 2 months of age. She had normal-appearing female genitalia and a karyotype of 46, XY. The serum cortisol and adrenal steroids levels were always nearly undetectable, but the adrenocorticotropic hormone levels were extremely high. Genetic analysis revealed compound heterozygous mutations at c. 229C > T (p.Q77X) in exon 3 and c. 722C > T (p.Q258X) in exon 7 of the StAR gene. The former mutation was previously detected in only two other Chinese CLAH patients. Both mutations cause truncation of the StAR protein. The case reported here appears to be a classic example of CLAH with very small adrenal glands and is the second reported CLAH case with small adrenal glands thus far. In a 15-year follow-up, the patient's height was approximately average for females before age 4 and fell to - 1 SDS at 10 years of age. Her bone age was similar to her chronological age from age 4 to age 15 years. CONCLUSIONS In conclusion, this is a classic case of CLAH with exceptionally small adrenal glands. Q77X mutation seems to be more common in Chinese CLAH patients. Additionally, this is the first report of the growth pattern associated with CLAH after a 15-year follow-up.
-
4.
A unique homozygous WRAP53 Arg298Trp mutation underlies dyskeratosis congenita in a Chinese Han family.
Shao, Y, Feng, S, Huang, J, Huo, J, You, Y, Zheng, Y
BMC medical genetics. 2018;(1):40
Abstract
BACKGROUND Dyskeratosis congenita (DC) is an inherited telomeropathy characterized by mucocutaneous dysplasia, bone marrow failure, cancer predisposition, and other somatic abnormalities. Cells from patients with DC exhibit short telomere. The genetic basis of the majority of DC cases remains unknown. METHODS A 2 generational Chinese Han family with DC was studied using targeted capture and next-generation sequencing to identify the underlying DC-related mutations. RESULTS In this study, we identified a unique homozygous WD repeat containing antisense to TP53 (WRAP53) Arg298Trp mutation in the proband with DC and heterozygous WRAP53 Arg298Trp mutations in his asymptomatic, consanguineous parents and his sister, indicating an autosomal recessive inheritance mode. The proband with the homozygous WRAP53 Arg298Trp mutation had short telomere, classic clinical symptoms, and no response to danazol, glucocorticoid or cyclosporin A. CONCLUSIONS Thus, we reported for the first time that a unique homozygous WRAP53 mutation site underlies the development of DC.
-
5.
Type 4B hereditary hemochromatosis associated with a novel mutation in the SLC40A1 gene: A case report and a review of the literature.
Zhang, W, Lv, T, Huang, J, Ou, X
Medicine. 2017;(38):e8064
-
-
Free full text
-
Abstract
RATIONALE Hereditary hemochromatosis can be divided into HFE- and non-HFE-related based on genetic mutations in different genes. HFE-related hemochromatosis is the most common inherited genetic disease in European populations but rare in Asia-pacific region. Recently, non-HFE-related hemochromatosis has been reported in patients from the Asian countries. PATIENT CONCERNS We report the case of a 48-year-old Chinese Han woman who presented with abnormal liver function, diabetes mellitus, hyperferritinemia, and high transferrin saturation, with severe iron overload in parenchymal cells, Kupffer cells, and periportal fibrosis on liver biopsy. No secondary factor for iron overload was identified. DIAGNOSES Sanger sequencing was conducted for the screening of mutation in the hereditary hemochromatosis related genes. The functional effect of a splicing mutation, SLC40A1 IVS 3+10 del gtt, was assessed by reverse-polymerase chain reaction analysis for SLC40A1 mRNA level, and by immunohistochemistry analysis of liver biopsy for ferroportin expression and cellular localization. OUTCOMES A novel splicing mutation IVS 3+10 del gtt was identified in the SLC40A1 gene. Functional analysis showed that IVS 3+10 del gtt in the SLC40A1 gene lead to a substantial reduction in the basal levels of SLC40A1 mRNA and increased membrane localization of ferroportin. Finally, the patient was diagnosed as ferroportin disease (type 4B hemochromatosis). LESSONS The present study is the first report to identify a classical splicing mutation in the SLC40A1 gene in type 4B hemochromatosis, and provide further evidence of the prevalence of type 4 hereditary hemochromatosis in Asian countries.
-
6.
TSC1 R509X Mutation in a Chinese Family with Tuberous Sclerosis Complex.
Zhang, Y, Gan, J, Pu, Z, Xu, Mm, Wang, Lf, Li, Yh, Liu, Zg
Neuromolecular medicine. 2015;(2):202-8
Abstract
Tuberous sclerosis complex is a rare autosomal dominant disorder caused by mutations in either of TSC1 and TSC2 genes. Tuberous sclerosis complex presents diverse clinical characteristics, and either of TSC1 and TSC2 genes shows a wide range of mutations in their coding regions. However, the correlation between genotype and phenotype is yet unknown. We describe the clinical characteristics of a Chinese family with TSC1 gene mutation and present a literature review of Chinese patients with tuberous sclerosis complex gene mutation reported since 2004. This is the first report of TSC1 R509X mutation in a Chinese family, which might deepen our insight into the clinical and molecular pathogenesis of tuberous sclerosis complex.
-
7.
Identification of a novel missense mutation of MAF in a Japanese family with congenital cataract by whole exome sequencing: a clinical report and review of literature.
Narumi, Y, Nishina, S, Tokimitsu, M, Aoki, Y, Kosaki, R, Wakui, K, Azuma, N, Murata, T, Takada, F, Fukushima, Y, et al
American journal of medical genetics. Part A. 2014;(5):1272-6
Abstract
Congenital cataracts are the most important cause of severe visual impairment in infants. Genetic factors contribute to the disease development and 29 genes are known to cause congenital cataracts. Identifying the genetic cause of congenital cataracts can be difficult because of genetic heterogeneity. V-maf avian musculoaponeurotic fibrosarcoma oncogene homolog (MAF) encodes a basic region/leucine zipper transcription factor that plays a key role as a regulator of embryonic lens fiber cell development. MAF mutations have been reported to cause juvenile-onset pulverulent cataract, microcornea, iris coloboma, and other anterior segment dysgenesis. We report on six patients in a family who have congenital cataracts were identified MAF mutation by whole exome sequencing (WES). The heterozygous MAF mutation Q303L detected in the present family occurs in a well conserved glutamine residue at the basic region of the DNA-binding domain. All affected members showed congenital cataracts. Three of the six members showed microcornea and one showed iris coloboma. Congenital cataracts with MAF mutation exhibited phenotypically variable cataracts within the family. Review of the patients with MAF mutations supports the notion that congenital cataracts caused by MAF mutations could be accompanied by microcornea and/or iris coloboma. WES is a useful tool for detecting disease-causing mutations in patients with genetically heterogeneous conditions.
-
8.
Erythroid transcription factor EKLF/KLF1 mutation causing congenital dyserythropoietic anemia type IV in a patient of Taiwanese origin: review of all reported cases and development of a clinical diagnostic paradigm.
Jaffray, JA, Mitchell, WB, Gnanapragasam, MN, Seshan, SV, Guo, X, Westhoff, CM, Bieker, JJ, Manwani, D
Blood cells, molecules & diseases. 2013;(2):71-5
-
-
Free full text
-
Abstract
KLF1 is an erythroid specific transcription factor that is involved in erythroid lineage commitment, globin switching and terminal red blood cell maturation. Various mutations of KLF1 have been identified in humans, which have led to both benign and pathological phenotypes. The E325K mutation, within the second zinc finger of the KLF1 gene, has been shown to cause a new form of congenital dyserythropoietic anemia (CDA) now labeled as CDA type IV. We report the fourth documented case of this mutation, and propose a clinical diagnostic model to better identify this disease in other patients. Our patient is a Taiwanese child who presented to us at 8years of age with severe hemolytic anemia, splenomegaly, elevated fetal hemoglobin (HbF), iron overload, and dyserythropoiesis in the bone marrow. KLF1 sequence analysis revealed a G-to-A transition in one allele of exon 3, which resulted in the substitution of a glutamate 325 by a lysine. Flow cytometry analysis revealed decreased protein expression of CD44 on the red blood cells, and decreased red blood cell deformability as measured using an ektacytometer. Blood typing revealed his red blood cells to be Co(a-b-), In(b-), LW(ab-) and Lu(b+), even though DNA testing predicted that he would be Co(a+b-) and LW(a+b-). This newly discovered CDA combines features of a hemoglobinopathy, RBC membrane defect and hereditary persistence of HbF (HPFH) which are not seen in the previous types of CDA. Increased awareness of this phenotype may improve the more prompt and accurate diagnosis of these patients.
-
9.
Phenotypes and genotypes of patients with pantothenate kinase-associated neurodegeneration in Asian and Caucasian populations: 2 cases and literature review.
Lee, CH, Lu, CS, Chuang, WL, Yeh, TH, Jung, SM, Huang, CL, Lai, SC
TheScientificWorldJournal. 2013;:860539
Abstract
OBJECTIVES Pantothenate kinase-associated neurodegeneration (PKAN) is a rare disease caused by pantothenate kinase 2 (PANK2, OMIM 606157) mutations. This study is aimed to investigate clinical presentations, pathologies, and genetics in patients with PKAN. METHODS Two patients with PKAN were reported. We reviewed the literature to include additional 19 patients with PKAN in Eastern Asia. These patients were divided into classic and atypical groups by the age of onset. We compared the data on PKAN patients of Asian and Caucasian populations. RESULTS We found iron deposits in the globus pallidus in our Patient 1 and a heterozygous truncating mutation (c.1408insT) in Patient 2. Literature review shows that generalized dystonia and bulbar signs are more common in classic PKAN patients, whereas segmental dystonia and tremors are more specific to atypical ones. Asian patients have less complex presentations--lower prevalence of pyramidal signs, mental impairment, and parkinsonism--than Caucasians. D378G in exon 3 is the most frequent mutation (28%) in Asians. CONCLUSIONS Our study demonstrates that the distribution of dystonia is the major distinction between subgroups of PKAN. Caucasian patients have more complex presentations than Asians. Exon 3 and 4 are hot spots for screening PANK2 mutations in Asian patients.