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Ambiguous genitalia is seen as the most common phenotypic reflection of sexual development disorders. Congenital adrenal hyperplasia (CAH) is the most common cause of ambiguous genitalia, while the most common cause of CAH is a 21-hydroxylase deficiency with a rate of 90-95%. The disease is caused by mutations in the CYP21A2 gene located at 6p21.3. It is inherited in an autosomal recessive manner. Seven previously identified point mutations, an 8-bp deletion and large deletions, have significant role in the etiology of the disease. In this study, we aimed to report CYP21 molecular genetic evaluation by RFLP and MLPA methods in classic CAH patients with 21-hydroxylase deficiency. In this study, 26 patients with pre-diagnosis of Classic Type Congenital Adrenal Hyperplasia due to 21-Hydroxylase deficiency were reported. Seven previously identified point mutations, an 8-bp deletion, and large deletions were analyzed by PCR-RFLP methods in the patient group. For the MLPA study, SALSA MLPA KIT P050-B2 CAH (Lot0408) kit which was produced by MRC Holland was used. In 21 (80.7%) of 26 patients analyzed, causative mutations were found. The most frequent mutation was the large deletions (6 patients, 12 allels), accounting 23% of the patients. In 21 (80.7%) of 26 patients, the causative mutations were found by using PCR (8-bp del. and large deletions) and RFLP (7 known point mutations) methods. MLPA analysis confirmed all of the deletions detected by PCR-RFLP, and the 83% of the detectable point mutations with MLPA. A complete genotype-phenotype relationship could be established in all patients in whom mutation could be detected in the study group. [ABSTRACT FROM AUTHOR]

A novel TECTA mutation, p.R1890C, was found in a Dutch family with nonsyndromic autosomal dominant sensorineural hearing impairment. In early life, presumably congenital, hearing impairment occurred in the midfrequency range, amounting to about 40 dB at 1 kHz. Speech recognition was good with all phoneme recognition scores exceeding 90%. An intact horizontal vestibuloocular reflex was found in four tested patients. The missense mutation is located in the zona pellucida (ZP) domain of α-tectorin. Mutations affecting the ZP domain of α-tectorin are significantly associated with midfrequency hearing impairment. Substitutions affecting other amino acid residues than cysteines show a significant association with hearing impairment without progression. Indeed, in the present family progression seemed to be absent. In addition, the presently identified mutation affecting the ZP domain resulted in a substantially lesser degree of hearing impairment than was previously reported for DFNA8/12 traits with mutations affecting the ZP domain of α-tectorin. [ABSTRACT FROM AUTHOR]

This study presents a broad overview of health issues and psychomotor development of 100 children with Angelman syndrome (AS), seen at the ENCORE Expertise Center for AS in Rotterdam, the Netherlands. We aimed to further delineate the phenotype of AS, to evaluate the association of the phenotype with genotype and other determinants such as epilepsy and to get insight in possible targets for intervention. We confirmed the presence of a more severe phenotype in the 15q11.2-q13 deletion subtype. Novel findings were an association of (early onset of) epilepsy with a negative effect on development, a high occurrence of nonconvulsive status epilepticus, a high rate of crouch gait in the older children with risk of deterioration of mobility, a relatively low occurrence of microcephaly, a higher mean weight for height in all genetic subtypes with a significant higher mean in the nondeletion children, and a high occurrence of hyperphagia across all genetic subtypes. Natural history data are needed to design future trials. With this large clinical cohort with structured prospective and multidisciplinary follow-up, we provide unbiased data on AS to support further intervention studies to optimize outcome and quality of life of children with AS and their family., (© 2019 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals, Inc.)