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Mutation of fibulin-1 causes a novel syndrome involving the central nervous system and connective tissues.

ABSTRACT: Fibulin-1 is an extracellular matrix protein that has an important role in the structure of elastic fibers and basement membranes of various tissues. Using homozygosity mapping and exome sequencing, we discovered a missense mutation, p.(Cys397Phe), in fibulin-1 in three patients from a consanguineous family presented with a novel syndrome of syndactyly, undescended testes, delayed motor milestones, mental retardation and signs of brain atrophy. The mutation discovered segregated with the phenotype and was not found in 374 population-matched alleles. The affected cysteine is highly conserved across vertebrates and its mutation is predicted to abolish a disulfide bond that defines the tertiary structure of fibulin-1. Our findings emphasize the crucial role fibulin-1 has in development of the central nervous system and various connective tissues.

SUBMITTER: Bohlega S

PROVIDER: S-EPMC3992572 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Mutation of fibulin-1 causes a novel syndrome involving the central nervous system and connective tissues.

Bohlega Saeed S Al-Ajlan Huda H Al-Saif Amr A

European journal of human genetics : EJHG 20131002 5

Fibulin-1 is an extracellular matrix protein that has an important role in the structure of elastic fibers and basement membranes of various tissues. Using homozygosity mapping and exome sequencing, we discovered a missense mutation, p.(Cys397Phe), in fibulin-1 in three patients from a consanguineous family presented with a novel syndrome of syndactyly, undescended testes, delayed motor milestones, mental retardation and signs of brain atrophy. The mutation discovered segregated with the phenoty ...[more]

PMID: 24084572

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