A novel compound heterozygous mutation of the L2HGDH gene in a Chinese boy with L-2-hydroxyglutaric aciduria: case report and literature review

Background: Hoyeraal–Hreidarsson syndrome (HHS) is considered a clinically severe variant of dyskeratosis congenita (DKC) and represents the extreme phenotype caused by aberrant telomere biology. Unlike patients with DKC who present later in life, most cases of HHS present in the first years of life. Clinical features include intrauterine growth restriction and microcephaly, which are universal but not pathognomonic, as well as gastrointestinal, immunological and neurological manifestations. The immunological profile is varied as a result of cellular immunodeficiency, humoral defects, or both, and may be the presenting symptom of these patients. Moreover, the immunological phenotype can change over time, making HHS a diagnostic challenge. Methods: This case report highlights the clinical presentation and immune investigations of a male patient with a novel mutation in DKC1, causing HHS. Results: Here, we describe a patient with HHS who presented with Pneumocystis jiroveci pneumonia and low T cells, which is typical of severe combined immunodeficiency. Over time, he developed agammaglobulinemia whereas T-cell function improved. He also presented with extremely severe gastrointestinal manifestations, and died at 3 years of age. Conclusion: This case report highlights a novel compound heterozygous mutation in DKC1, and the need to consider HHS as the differential diagnosis of patients with combined immunodeficiency. Statement of novelty: The case reports on a novel mutation in DKC1.

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Genotypic and phenotypic character of Chinese neonates with congenital protein C deficiency: a case report and literature review

Thrombosis Journal ◽

10.1186/s12959-019-0208-6 ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 1

Author(s):

Xiaoying Li ◽

Xiaoyan Li ◽

Xiao Li ◽

Yuanhua Zhuang ◽

Lili Kang ◽

...

Keyword(s):

Literature Review ◽

Protein C ◽

Molecular Genetic ◽

Purpura Fulminans ◽

Protein S ◽

Compound Heterozygous Mutation ◽

Heterozygous Mutation ◽

Molecular Testing ◽

Compound Heterozygous ◽

Protein C Deficiency

Abstract Background Our objective was to study the phenotype of and molecular genetic mechanisms underlying congenital protein C (PC) deficiency in Chinese neonates. We report the case of a neonate who presented 4 h after birth with purpura fulminans of the skin and thrombosis in the kidney. We also carried out a through literature review to study the genotype and phenotype, relevance, diagnosis, management, and prognosis of neonates with congenital PC deficiency in China. Case presentation and literature review Following a septic work-up and check of PC and protein S (PS) levels that showed PC deficiency, we investigated the patient’s and her parents’ genotypes. Our patient was found to have a plasma PC level of 0.8%. Molecular testing revealed a compound heterozygous mutation of the PROC gene: From the father, a c._262 G > T p. ASP88Tyr mutation in exon 4; from the mother, a C. 400 + 5G mutation in intron 5 that had been previously reported as likely pathogenic. Both parents were found to have heterozygous mutations for PC deficiency. In China, 5 other cases of congenital PC deficiency in the neonatal period were reported in the literature. In those cases, purpura fulminans and thrombosis were the main symptoms, and homozygous or compound heterozygous mutations of the PROC gene were identified. Conclusion Congenital PC deficiency should be ruled out for neonates presenting with purpura fulminans and thrombosis.

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A Chinese patient with 11β-hydroxylase deficiency due to novel compound heterozygous mutation in CYP11B1 gene: a case report

BMC Endocrine Disorders ◽

10.1186/s12902-018-0295-6 ◽

2018 ◽

Vol 18 (1) ◽

Cited By ~ 1

Author(s):

Xianxian Yuan ◽

Lin Lu ◽

Shi Chen ◽

Jun Jiang ◽

Xiangqing Wang ◽

...

Keyword(s):

Case Report ◽

Chinese Patient ◽

Compound Heterozygous Mutation ◽

Heterozygous Mutation ◽

Compound Heterozygous ◽

Hydroxylase Deficiency

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A Novel Compound Heterozygous Mutation in the WFS1 Gene (C.1997 G>A and C.2113_2114 ins T) Causes wolfram Syndrome: A Case Report

10.21203/rs.3.rs-38184/v1 ◽

2020 ◽

Author(s):

Reyida Aishajiang ◽

Cheng Li ◽

Bo-Tao Shen ◽

Jian Sun ◽

Wei Zhao

Keyword(s):

Case Report ◽

Autosomal Recessive Disorder ◽

Later Life ◽

Wolfram Syndrome ◽

Compound Heterozygous Mutation ◽

Heterozygous Mutation ◽

Compound Heterozygous ◽

Sagittal Sinus ◽

Wfs1 Gene ◽

Tract Infections

Abstract Background:Wolfram syndrome (WS) is a rare autosomal recessive disorder associated with early-onset diabetes mellitus (DM), diabetes insipidus (DI), optic atrophy (OA) and hearing impairment. Most patients with WS have mutations in the WFS1 gene, which encodes wolframin. This case report describes a patient with a novel heterozygous mutation of WFS1.Case Presentation:The proband was a 27-year-old Chinese male with WS who had developed DM at the age of 2 years, DI in the first decade, OA, neurogenic bladder and urinary tract infections in the second decade, and neurological abnormalities in later life. Magnetic resonance imaging suggested superior sagittal sinus enlargement and atrophy of the medulla and pons. Sequencing showed that the proband’s asymptomatic parents were both carriers: the father carried a heterozygous c.1997G>A mutation that creates a premature stop at codon 666 (W666X) and that the proband’s asymptomatic mother carried a heterozygous c.2113_2114insT mutation that generates a frameshift downstream to codon 705 (K705Ifs*7) and leads to a stop at codon 711. The proband had both the above C-terminal mutations, resulting in the substitution of N-glycosylation sitesthat are associated with the stability of wolframin.Conclusion:We have identified a novel compound heterozygous mutation of WFS1 that is associated with WS. Our findings may facilitate future screening of WS carriers.

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