scholarly journals Case report: Compound heterozygous mutations in AP4M1 gene identified in a Chinese infant with Infantile Spasms and Global developmental delay

2021 ◽  
Author(s):  
Lily Zhang ◽  
Xingbing Jin ◽  
Yaqin Wang ◽  
Yan He ◽  
Haoyu Li
Keyword(s):  
Developmental Delay ◽  
Membrane Trafficking ◽  
Protein Complex ◽  
Adaptor Protein ◽  
Infantile Spasms ◽  
Chinese Patient ◽  
Global Developmental Delay ◽  
Compound Heterozygous ◽  
First Case ◽  
Compound Heterozygous Mutations

Abstract Background: Adaptor protein complex-4 (AP-4), a heterotetrameric protein complex, plays an important role in vesicle trafficking in neurons. Mutations in genes affecting different subunits of AP-4, including AP4B1, AP4E1, AP4S1, and AP4M1, have been recently associated with spastic tetraplegia, developmental delay and intellectual disability (ID).Case presentation: We report on a Chinese patient with infantile spasms, infantile hypotonia and global developmental delay. Exome sequencing showed compound heterozygous mutations in AP4M1(c.19A>G, p.I7V and c.137C>T, p.P46L).Conclusions: This is the first case of biallelic missense variants lay on the region encoding LH domain, which is important for membrane trafficking via protein–protein and intramolecular binding specificities. Our study expands the molecular spectrum associated with AP-4 deficiency syndrome, and reviews the clinical features of reported patients with AP4M1 mutations.

scholarly journals Novel compound heterozygous mutations in WDR62 gene leading to developmental delay and Primary Microcephaly in Saudi Family

2019 ◽  
Vol 35 (3) ◽  
Author(s):  
Muhammad Imran Naseer ◽  
Mahmood Rasool ◽  
Angham Abdulrahman Abdulkareem ◽  
Adeel G. Chaudhary ◽  
Syed Kashif Zaidi ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
Genetic Defect ◽  
Compound Heterozygous ◽  
Sequencing Analysis ◽  
The Novel ◽  
Primary Microcephaly ◽  
Saudi Family ◽  
Exon 9 ◽  
Compound Heterozygous Mutations

Objective: Primary microcephaly (MCPH) is a rare autosomal recessive disorder characterized by impaired congenital reduction of brain size along with head circumference and intellectual disability. MCPH is a heterogeneous disorder and more than twenty four genes associated with this disease have been identified so far. The objective of this study was to find out the novel genes or mutations leading to the genetic defect in a Saudi family with primary microcephaly. Methods: Whole exome sequencing was carried out to find the novel mutation and the results was further validated using Sanger sequencing analysis. This study was done in the Center of excellence in Genomic Medicine and Research, King Abdulaziz University under KACST project during 2017 and 2018. Results: We report a novel compound heterozygous mutations c.797C>T in exon 7 and c.1102G>A in exon 9 of the WD repeat domain 62 (WDR62) (OMIM 604317) gene in two affected siblings in Saudi family with intellectual disability, speech impediments walking difficulty along with primary microcephaly. Two rare, missense variants were detected in heterozygous state in the WDR62 gene in these two affected individuals from the heterozygous parents. Conclusions: A compound heterozygous mutations c.797C>T in exon 7 and c.1102G> A in exon 9 of the WDR62 gene was identified. WDR62 gene is very important gene and mutation can lead to neuro developmental defects, brain malformations, reduced brain and head size. These results should be taken into consideration during prognostic discussions and mutation spectrum with affected patients and their families in the Saudi population. doi: https://doi.org/10.12669/pjms.35.3.36 How to cite this:Naseer MI, Rasool M, Abdulkareem AA, Chaudhary AG, Zaidi SK, Al-Qahtani MH. Novel compound heterozygous mutations in WDR62 gene leading to developmental delay and Primary Microcephaly in Saudi Family. Pak J Med Sci. 2019;35(3):---------.  doi: https://doi.org/10.12669/pjms.35.3.36 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

scholarly journals Compound heterozygous mutations in the LTBP2 gene associated with microspherophakia in a Chinese patient: a case report and literature review

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Manhua Xu ◽  
Kaiming Li ◽  
Weimin He
Keyword(s):  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Chinese Patient ◽  
Western China ◽  
Compound Heterozygous ◽  
The Novel ◽  
Case Presentation ◽  
Ectopia Lentis ◽  
Compound Heterozygous Mutations ◽  
Next Generation Sequencing Ngs

Abstract Background Microspherophakia (MSP, OMIM 251,750) is a rare inherited autosomal recessive eye disorder characterized by small spherically shaped lens. Several studies have indicated that the transforming growth factor-beta (TGF-beta) binding proteins(LTBP2) gene mutation is the predominant cause of MSP. In our study, novel compound heterozygous mutations in the LTBP2 gene associated with MSP were reported, which was different from previous reported homozygous mutations. Case presentation The proband was an 18‐year‐old male in Western China with bilateral MSP, accompanied by ectopia lentis, secondary glaucoma and blindness in both eyes. In our hospital, he received bilateral lens resection and trabeculectomy combined with peripheral iridotomy. Using next-generation sequencing (NGS)-based gene panel tests, we identified pathogenic mutations in the peripheral blood DNA sample from the proband: c.3614_3618dupCTGGC (exon24, NM_000428) and c.2819G > A (exon18, NM_000428). The presence of the novel compound heterozygous mutations in the LTBP2 gene was linked with the development of MSP. Sanger sequencing confirmed the existence of one of the two variants in each parent respectively. Conclusion Our results demonstrated a rare case of MSP phenotype associated with novel compound heterozygous mutations in the LTBP2 gene using NGS technology.

scholarly journals The Novel Compound Heterozygous Mutations of GAA Gene in Mainland Chinese Patient with Classic Infantile-Onset Pompe Disease

2020 ◽  
Vol 61 (1) ◽  
pp. 178-182
Author(s):  
Jiaming Li ◽  
Yinghua Cui ◽  
Xin Wang ◽  
Qinglei Wang ◽  
Hongjun Wang ◽  
...  
Keyword(s):  
Pompe Disease ◽  
Chinese Patient ◽  
Compound Heterozygous ◽  
The Novel ◽  
Mainland Chinese ◽  
Compound Heterozygous Mutations ◽  
Gaa Gene

A first case report of UDP-galactose-4′-epimerase deficiency in China: genotype and phenotype

2016 ◽  
Vol 29 (3) ◽  
Author(s):  
Fan Tong ◽  
Rulai Yang ◽  
Fang Hong ◽  
Guling Qian ◽  
Pingping Jiang ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Chinese Population ◽  
Novel Mutation ◽  
Total Bile Acid ◽  
Glutamyl Endopeptidase ◽  
Compound Heterozygous ◽  
Normal Range ◽  
Powdered Milk ◽  
First Case ◽  
Compound Heterozygous Mutations

AbstractThe aim of the study was to investigate the incidence and genotype-phenotype characteristics of UDP-galactose-4′-epimerase (GALE) deficiency in newborn screening of Chinese population.Neonates were screened at the Newborn Screening Center of Zhejiang Province, China for GALE deficiency and their condition was confirmed by testing of theA total of 350,023 of newborns were screened; of which, the condition of one female neonate was diagnosed with GALE deficiency, accounting for an incidence rate of approximately 1:350,000 in our sample. The patient with GALE deficiency clinically manifested slight increase in levels of blood galactose (122–251 mg/L), glutamyl endopeptidase (61 U/L), total bile acid (17 μmol/L), and lactic acid (1.8 mmol/L). The neonate was fed with lactose-free powdered milk and followed-up to 1 year. Re-examination showed that all biochemical indicators recovered to normal range, whereas physical and mental development appeared normal without cataract change. The genotype of GALE deficiency was identified as compound heterozygous mutations: c.505C>T (p.R169W) and c.452G>A (p.G151D). The latter was a novel mutation. The GALE enzyme value was 42% of control.GALE deficiency is relatively rare in China. The genotype of compound heterozygous mutations at R169W and G151D clinically manifest as mild-type; it is recommended to limit galactose diet.

scholarly journals Case Report: A Novel Compound Heterozygous Mutation of the FRMD4A Gene Identified in a Chinese Family With Global Developmental Delay, Intellectual Disability, and Ataxia

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuhua Pan ◽  
Xiaoling Guo ◽  
Xiaoqiang Zhou ◽  
Yue Liu ◽  
Jingli Lian ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Intellectual Development ◽  
Scaffolding Protein ◽  
Compound Heterozygous Mutation ◽  
Global Developmental Delay ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Missense Mutations ◽  
Sequencing Data

Background: FERM domain-containing protein 4A (FRMD4A) is a scaffolding protein previously proposed to be critical in the regulation of cell polarity in neurons and implicated in human intellectual development.Case Presentation: We report a case of a 3-year-old boy with corpus callosum anomaly, relative macrocephaly, ataxia, and unexplained global developmental delay. Here, compound heterozygous missense mutations in the FRMD4A gene [c.1830G>A, p.(Met610Ile) and c.2973G>C, p.(Gln991His)] were identified in the proband, and subsequent familial segregation showed that each parent had transmitted a mutation.Conclusions: Our results have confirmed the associations of mutations in the FRMD4A gene with intellectual development and indicated that for patients with unexplained global developmental delay, the FRMD4A gene should be included in the analysis of whole exome sequencing data, which can contribute to the identification of more patients affected by this severe phenotypic spectrum.

Vitamin B12 Deficiency in Children With Infantile Spasms: A Case-Control Study

2018 ◽  
Vol 33 (12) ◽  
pp. 767-771 ◽  
Author(s):  
Mahender K. Meena ◽  
Suvasini Sharma ◽  
Himani Bhasin ◽  
Puneet Jain ◽  
Seema Kapoor ◽  
...  
Keyword(s):  
Standard Deviation ◽  
Developmental Delay ◽  
Methylmalonic Acid ◽  
Case Reports ◽  
Serum Vitamin ◽  
Infantile Spasms ◽  
Global Developmental Delay ◽  
P Value ◽  
Vitamin B ◽  
Serum Homocysteine

There have been few case reports showing association of vitamin B12 deficiency with infantile spasms. We planned this study to see if there was an association of serum vitamin B12 deficiency in children with development of infantile spasms. Cases included children with infantile spasms of ages 6 months to 3 years. The controls were children in the same age group who had global developmental delay but no history of epileptic spasms. Mean serum vitamin B12, serum homocysteine, and urinary methylmalonic acid levels were measured in both groups and compared. Children with infantile spasms had lower mean serum vitamin B12 levels (354.1 pg/mL; standard deviation 234.1 pg/mL) as compared to children with global developmental delay without spasms (466.7 pg/mL; standard deviation 285.5 pg/mL) ( P value < .05). Mean serum homocysteine level (13.9 vs 7.8 μmol/L, P = .02) and mean urinary methylmalonic acid level (68.1 mmol/mol of creatinine vs 26.1 mmol/mol of creatinine, P = .03) were elevated in children with infantile spasms than in controls. Fourteen children (35.0%) with infantile spasms were vitamin B12 deficient compared with 3 (7.50%) controls ( P = .005). Thus, vitamin B12 deficiency may have an association with infantile spasms. More studies are needed before recommending routine measurement of serum B12 levels in children with infantile spasms.

Identification of two novel TPK1 gene mutations in a Chinese patient with thiamine pyrophosphokinase deficiency undergoing whole exome sequencing

2019 ◽  
Vol 32 (3) ◽  
pp. 295-300 ◽  
Author(s):  
Lina Zhu ◽  
Ruijuan Wu ◽  
Zhenlong Ye ◽  
Ruijie Gu ◽  
Yongxia Wang ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Normal Level ◽  
Chinese Patient ◽  
Chinese Patients ◽  
Compound Heterozygous ◽  
Heterozygous Carrier ◽  
Whole Exome ◽  
Compound Heterozygous Mutations ◽  
The Brain

Abstract Background The mutations of thiamine pyrophosphokinase-1 (TPK1) gene have been frequently studied in some patients with thiamine metabolism dysfunction syndrome-5 (THMD5), while TPK1 mutations in Chinese patients have been investigated by only homozygous. A search of the literature on the mutations in the Chinese population currently published revealed that no reports of compound heterozygous mutations were reported. Here, we report a Chinese patient with compound heterozygous TPK1 mutations who underwent magnetic resonance imaging (MRI), whole exome sequencing (WES), molecular diagnosis, bioinformatics analysis, and three-dimensional (3D) protein structure analysis. Case presentation A Chinese boy was born after an uneventful pregnancy to non-consanguineous and healthy parents. On the sixth day after his birth, the lactate level of the patient was between 8.6 mmol/L and 14.59 mmol/L in plasma (the normal level is in the range of 0.5–2.2 mmol/L). Lactate was reduced to the normal level after rehydration, acid correction, expansion, and other treatments. After 4 months, the patient presented with an acute, 3-h-long, non-induced convulsions, and was admitted to our hospital for weakness, decreased oral intake, and lethargy. Results achieved by electroencephalography (EEG), cerebrospinal fluid, and other biochemical findings were normal. A visible hemorrhagic lesion was also observed in the brain. Seizures increased significantly during infection, which was accompanied by higher lactic acid levels. MRI of the brain showed an obvious signal shadow, in which bilateral frontal and temporal parietal subarachnoid cavities were widened, and more abnormal signals were observed; therefore, further consideration of hypoxic-ischemic encephalopathy and genetic metabolic disease was taken into account. Conclusions The results of WES revealed that the patient was associated with compound heterozygous mutations NM_022445.3:c.[263G>A]; [226A>G] of TPK1. His parents were non-consanguineous; while his father was found to be a heterozygous carrier with the mutation c.[263G>A], his mother was identified as a heterozygous carrier with the mutation c.[226A>G]. The results indicated that the patient had a compound heterozygous TPK1 mutation, and this is the first reported case in China.

scholarly journals Case Report: Complete Maternal Uniparental Disomy of Chromosome 2 With a Novel UNC80 Splicing Variant c.5609-4G> A in a Chinese Patient With Infantile Hypotonia With Psychomotor Retardation and Characteristic Facies 2

2021 ◽  
Vol 12 ◽  
Author(s):  
Yilun Tao ◽  
Dong Han ◽  
Yiju Wei ◽  
Lihong Wang ◽  
Wenxia Song ◽  
...  
Keyword(s):  
Case Report ◽  
Developmental Delay ◽  
Autosomal Recessive ◽  
Snp Array ◽  
Uniparental Disomy ◽  
Psychomotor Retardation ◽  
Chinese Patient ◽  
Global Developmental Delay ◽  
Chromosome 2 ◽  
Splicing Variant

Background: Infantile hypotonia with psychomotor retardation and characteristic facies 2 (IHPRF2) is a rare autosomal recessive neurodevelopmental disorder caused by mutations in the UNC80 gene. It is characterized by severe global developmental delay, poor or absent speech and absent or limited walking abilities. The current study explored a case of a Chinese patient with IHPRF2 caused by a novel splicing variant of UNC80.Case Report: The proband is a 8-year-old Chinese male manifested with global developmental delay, severe truncal hypotonia, absent speech and intellectual disability. SNP array analysis revealed a uniparental isodisomy of the entire chromosome 2 [UPD(2)] in the proband. Whole exome sequencing (WES) subsequently identified a novel mutation c.5609-4G&gt;A in the UNC80 gene, which was inherited from his mother and was confirmed by Sanger sequencing, indicating that UPD(2) was of maternal origin.Conclusion: A novel UNC80 homozygous splicing variant c.5609-4G&gt;A associated with maternal UPD(2) was identified. These findings indicate that UPD poses a high risk of autosomal recessive diseases, and provides information on the variant spectrum for UNC80. Our findings elucidate on understanding of the genotype-phenotype associations that occur in IHPRF2 patients.

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