MASP1 mutations in patients with facial, umbilical, coccygeal, and auditory findings of carnevale, malpuech, OSA, and michels syndromes

Asli Sirmaci, Tom Walsh, Hatice Akay, Michail Spiliopoulos, Yildirim Bayezit Şakalar, Aylin Hasanefendioǧlu-Bayrak, Duygu Duman, Amjad Farooq, Mary Claire King, Mustafa Tekin

Research output: Contribution to journalArticle

91 Scopus citations

Abstract

Distinctive facial features consisting of hypertelorism, telecanthus, blepharophimosis, blepharoptosis, epicanthus inversus, periumbilical defects, and skeletal anomalies are seen in autosomal-recessive Carnevale, Malpuech, Michels, and oculo-skeletal-abdominal (OSA) syndromes. The gene or genes responsible for these syndromes were heretofore unknown. We report on three individuals from two consanguineous Turkish families with findings characteristic of these syndromes, including facial dysmorphism, periumbilical depression, mixed hearing loss, radioulnar synostosis, and coccygeal appendage. Homozygosity mapping yielded an autozygous region on chromosome 3q27 in both families. In one family, whole exome sequencing revealed a missense mutation, MASP1 c.2059G>A (p.G687R), that cosegregated with the phenotype. In the second family, Sanger sequencing of MASP1 revealed a nonsense mutation, MASP1 c.870G>A (p.W290X), that also cosegregated with the phenotype. Neither mutation was found in 192 Turkish controls or 1200 controls of various other ancestries. MASP1 encodes mannan-binding lectin serine protease 1. The two mutations occur in a MASP1 isoform that has been reported to process IGFBP-5, thereby playing a critical role in insulin growth factor availability during craniofacial and muscle development. These results implicate mutations of MASP1 as the cause of a human malformation syndrome and demonstrate the involvement of MASP1 in facial, umbilical, and ear development during the embryonic period.

Original languageEnglish (US)
Pages (from-to)679-686
Number of pages8
JournalAmerican journal of human genetics
Volume87
Issue number5
DOIs
StatePublished - Nov 12 2010

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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