MMACHC gene mutation in familial hypogonadism with neurological symptoms.
Recent studies have convincingly documented that hypogonadism is a component of various hereditary disorders and is often recognized as an important clinical feature in combination with various neurological symptoms, yet, the causative genes in a few related families are still unknown. High-throughput sequencing has become an efficient method to identify causative genes in related complex hereditary disorders. In this study, we performed exome sequencing in a family presenting hypergonadotropic hypogonadism with neurological presentations of mental retardation, epilepsy, ataxia, and leukodystrophy. After bioinformatic analysis and Sanger sequencing validation, we identified compound heterozygous mutations: c.482G>A (p.R161Q) and c.609G>A (p.W203X) in MMACHC gene in this pedigree. MMACHC was previously confirmed to be responsible for methylmalonic aciduria (MMA) combined with homocystinuria, cblC type (cblC disease), a hereditary vitamin B12 metabolic disorder. Biochemical and gas chromatography-mass spectrometry (GC-MS) examinations in this pedigree further supported the cblC disease diagnosis. These results indicated that hypergonadotropic hypogonadism may be a novel clinical manifestation of cblC disease, but more reports on additional patients are needed to support this hypothesis.
Department of Neurology, The first affiliated Hospital of Zhengzhou University, Zhengzhou University. 1 Jian-she East Road, Zhengzhou 450000, Henan, China.
Changhe
C
Shi
Department of Neurology, The first affiliated Hospital of Zhengzhou University, Zhengzhou University. 1 Jian-she East Road, Zhengzhou 450000, Henan, China.
Dandan
D
Shang
Department of Neurology, The first affiliated Hospital of Zhengzhou University, Zhengzhou University. 1 Jian-she East Road, Zhengzhou 450000, Henan, China.
Shilei
S
Sun
Department of Neurology, The first affiliated Hospital of Zhengzhou University, Zhengzhou University. 1 Jian-she East Road, Zhengzhou 450000, Henan, China.
Chengyuan
C
Mao
Department of Neurology, The first affiliated Hospital of Zhengzhou University, Zhengzhou University. 1 Jian-she East Road, Zhengzhou 450000, Henan, China.
Jie
J
Qin
Department of Neurology, The first affiliated Hospital of Zhengzhou University, Zhengzhou University. 1 Jian-she East Road, Zhengzhou 450000, Henan, China.
Haiyang
H
Luo
Department of Endocrinology, The first affiliated Hospital of Zhengzhou University, Zhengzhou University. 1 Jian-she East Road, Zhengzhou 450000, Henan, China.
Mingwei
M
Shao
Department of Ultrasound, The first affiliated Hospital of Zhengzhou University, Zhengzhou University. 1 Jian-she East Road, Zhengzhou 450000, Henan, China.
Zhengguang
Z
Chen
Department of Neurology, The first affiliated Hospital of Zhengzhou University, Zhengzhou University. 1 Jian-she East Road, Zhengzhou 450000, Henan, China.
Yutao
Y
Liu
Department of Neurology, The first affiliated Hospital of Zhengzhou University, Zhengzhou University. 1 Jian-she East Road, Zhengzhou 450000, Henan, China.
Xinjing
X
Liu
Department of Neurology, The first affiliated Hospital of Zhengzhou University, Zhengzhou University. 1 Jian-she East Road, Zhengzhou 450000, Henan, China.
Bo
B
Song
Department of Neurology, The first affiliated Hospital of Zhengzhou University, Zhengzhou University. 1 Jian-she East Road, Zhengzhou 450000, Henan, China. Electronic address: xuyuming@zzu.edu.cn.
Yuming
Y
Xu
D000328:Adult; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D006801:Humans; D007006:Hypogonadism / Q000150:complications / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009422:Nervous System Diseases / Q000150:complications / Q000235:genetics*; D010088:Oxidoreductases; D010375:Pedigree
D002352:Carrier Proteins; C508359:MMACHC protein, human; D010088:Oxidoreductases
Homocystinuria; Hypogonadism; MMACHC; Methylmalonic aciduria; cblC