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Molecular neonatal screening for homocystinuria in the Qatari population
Author(s) -
Zschocke Johannes,
Kebbewar Moustafa,
GanSchreier Hongying,
Fischer Christine,
FangHoffmann Junmin,
Wilrich Julia,
Abdoh Ghassan,
BenOmran Tawfeg,
Shahbek Noora,
Lindner Martin,
Al Rifai Hilal,
Al Khal Abdul Latif,
Hoffmann Georg F.
Publication year - 2009
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20994
Subject(s) - homocystinuria , biology , cystathionine beta synthase , genetics , population , mutation , allele , newborn screening , allele frequency , gene , medicine , methionine , amino acid , environmental health
We report the results of molecular neonatal screening for homocystinuria (cystathionine beta‐synthase deficiency) in neonates of Qatari origin, developed in conjunction with a novel biochemical screening approach. DNA was extracted from dried blood spots (DBS); the prevalent Qatari CBS gene mutation p.R336C (c.1006C>T) and a second mutation were tested with specific TaqMan assays. Over a period of 2 years we screened 12,603 neonates and identified six affected neonates homozygous for p.R336C. There were 225 heterozygous carriers for p.R336C. One additional child with homocystinuria detected through biochemical screening was homozygous for a mutation not previously identified in Qatar. Homocystinuria in the Qatari population has an incidence of 1:1,800, the highest in the world and even higher than previously estimated. Allele frequency of the mutation p.R336C is approximately 1%, displaying a significant deviation from Hardy Weinberg equilibrium. In conclusion, first‐line molecular neonatal screening is technically feasible and may be developed as an option for presymptomatic identification of genetic disorders caused by specific mutations or a limited number of prevalent mutations. However, sensitivity for the diagnosis of disorders caused by various mutations is limited even in a homogeneous population such as Qatar. Hum Mutat 30:1–2, 2009. © 2009 Wiley‐Liss, Inc.