Details

Autor(en) / Beteiligte

• Rafiq, Muhammad Arshad
• Kuss, Andreas W.
• Puettmann, Lucia
• Noor, Abdul
• Ramiah, Annapoorani
• Ali, Ghazanfar
• Hu, Hao
• Kerio, Nadir Ali
• Xiang, Yong
• Garshasbi, Masoud
• Khan, Muzammil Ahmad
• Ishak, Gisele E.
• Weksberg, Rosanna
• Ullmann, Reinhard
• Tzschach, Andreas
• Kahrizi, Kimia
• Mahmood, Khalid
• Naeem, Farooq
• Ayub, Muhammad
• Moremen, Kelley W.
• Vincent, John B.
• Ropers, Hans Hilger
• Ansar, Muhammad
• Najmabadi, Hossein

Titel

Mutations in the Alpha 1,2-Mannosidase Gene, MAN1B1, Cause Autosomal-Recessive Intellectual Disability

Ist Teil von

• American journal of human genetics, 2011-07, Vol.89 (1), p.176-182

Ort / Verlag

Cambridge, MA: Elsevier Inc

Erscheinungsjahr

2011

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• We have used genome-wide genotyping to identify an overlapping homozygosity-by-descent locus on chromosome 9q34.3 (MRT15) in four consanguineous families affected by nonsyndromic autosomal-recessive intellectual disability (NS-ARID) and one in which the patients show additional clinical features. Four of the families are from Pakistan, and one is from Iran. Using a combination of next-generation sequencing and Sanger sequencing, we have identified mutations in the gene MAN1B1, encoding a mannosyl oligosaccharide, alpha 1,2-mannosidase. In one Pakistani family, MR43, a homozygous nonsense mutation (RefSeq number NM_016219.3: c.1418G>A [p.Trp473∗]), segregated with intellectual disability and additional dysmorphic features. We also identified the missense mutation c. 1189G>A (p.Glu397Lys; RefSeq number NM_016219.3), which segregates with NS-ARID in three families who come from the same village and probably have shared inheritance. In the Iranian family, the missense mutation c.1000C>T (p.Arg334Cys; RefSeq number NM_016219.3) also segregates with NS-ARID. Both missense mutations are at amino acid residues that are conserved across the animal kingdom, and they either reduce kcat by ∼1300-fold or disrupt stable protein expression in mammalian cells. MAN1B1 is one of the few NS-ARID genes with an elevated mutation frequency in patients with NS-ARID from different populations.