ABSTRACT
BACKGROUND AND AIM: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is a common autosomal recessive disorder. Our objective was to identify the 21-hydroxylase active gene, CYP21A2 mutations in Malaysian 21-OHD patients using different techniques. MATERIALS AND METHODS: Blood samples were obtained from 97 Malaysian 21-OHD patients, which included 40 siblings from 19 families. We used various techniques which include restriction enzyme digestion, Southern blot, multiple ligation-dependent probe amplification (MLPA) and sequencing to elucidate CYP21A2 mutations. RESULTS: Homozygous and compound heterozygous mutations were identified in 95 of the 97 patients (98%). Deletions of CYP21A2 were found in 43 patients (44.3%). Deletions identified in CYP21A2 gene were the usual 30-kb deletion comprising 3'UTR CYP21A1P, C4B and 5'CYP21A2, complete deletion of CYP21A2 gene, deletion in exons 1-3, exons 1-6 and exons 1-8 of CYP21A2. The common mutations identified in CYP21A2 gene were deletion/conversion (22.6%), p.R356W (22%), IVS2-13A/C>G (21.3%), p.I172N (5.3%), p.Q318X (5.3%), and p.P30L (1.03%). This is the first report of the mutation frequency in CYP21A2 gene among the Malay ethnic group. Two novel mutations, c.Y97insT and p.L345P were identified in our patients. Our results show good phenotype-genotype correlation in most of the cases, although clinical variations were identified in some patients. CONCLUSIONS: The study has found various mutations including deletions in CYP21A2 gene in Malaysian patients with 21-hydroxylase deficiency using the MLPA technique that is being widely used in present laboratory settings.
Subject(s)
Adrenal Hyperplasia, Congenital/genetics , Steroid 21-Hydroxylase/genetics , Adrenal Hyperplasia, Congenital/epidemiology , Base Sequence , Child , Child, Preschool , DNA Mutational Analysis , Family , Female , Gene Frequency , Humans , Infant , Malaysia/epidemiology , Male , Multiplex Polymerase Chain Reaction , Mutation/physiology , SiblingsABSTRACT
Anthropometric wrist measurement ratios were examined for an association with idiopathic carpal tunnel syndrome (CTS). Wrist measurements were recorded in 67 patients with CTS and in a matched control group of 67 healthy volunteers. The Wrist Ratio (WR) (wrist anterior to posterior dimension/wrist medial-lateral dimension) and the Wrist Palm Ratio (wrist anterior to posterior dimension/palm length) were calculated for each case. We found that a WR of > or =0.70 and a Wrist Palm Ratio of >0.342 were significantly associated with idiopathic CTS.
