当前位置： SCI文献检索 > JOURNAL OF THE NEUROLOGICAL SCIENCES期刊下所有文献 > Two families with novel missense mutations in COL4A1: When diagnosis can be missed.

Two families with novel missense mutations in COL4A1: When diagnosis can be missed.

Abstract：

:Mutations in COL4A1, encoding one of the six collagen type IV proteins, cover a wide spectrum of autosomal dominant overlapping phenotypes including porencephaly, small-vessel disease and hemorrhagic stroke, leukoencephalopathy, hereditary angiopathy with nephropathy, aneurysms and muscle cramp (HANAC) syndrome, and Walker-Warburg syndrome. Over 50 mutations are known, mainly being missense changes. Intra- and inter-familial variability has been reported. We studied two Italian families in which the proband had a clinical diagnosis of COL4A1-related disorder. We found two novel mutations (c.1249G>C; p.Gly417Arg and c.2662G>C; p.Gly888Arg). Both involved highly conserved amino acids and were predicted as being deleterious by bioinformatics tools. The c.1249G>C (p.Gly417Arg) segregated in four subjects with variable neurological phenotypes, namely leukoencephalopathy with muscle symptoms, brain small-vessel disease, and mild infantile encephalopathy. A fourth case was a carrier of the mutation without any neurological symptoms and an MRI with a specific white matter anomaly. The c.2662G>C (p.Gly888Arg) mutation was de novo in the proband. After a temporary motor impairment at age 14, the subject complained of mild imbalance at age 30, during the third trimester of her twin pregnancy, when an anomaly of the left brain hemisphere was documented in one fetus. Both her male dizygotic twins presented a severe motor delay, early convulsions, and leukoencephalopathy, and were carriers of the mutation. In summary, we confirm that high intra-familial variability of COL4A1 mutations with very mild phenotypes, the apparent incomplete penetrance, and de novo changes may become a "dilemma" for clinicians and genetic counselors.

journal_name

J Neurol Sci

journal_title

Journal of the neurological sciences

authors

Giorgio E,Vaula G,Bosco G,Giacone S,Mancini C,Calcia A,Cavalieri S,Di Gregorio E,Rigault De Longrais R,Leombruni S,Pinessi L,Cerrato P,Brusco A,Brussino A

doi

10.1016/j.jns.2015.03.042

subject

Has Abstract

pub_date

2015-05-15 00:00:00

pages

99-104

issue

1-2

eissn

0022-510X

issn

1878-5883

pii

S0022-510X(15)00189-6

journal_volume

352

pub_type

杂志文章

在线工具

Two families with novel missense mutations in COL4A1: When diagnosis can be missed.