Detailed mapping, mutation analysis, and intragenic polymorphism identification in candidate Noonan syndrome genes MYL2,DCN, EPS8, andRPL6

Editor—Since the initial case of partial trisomy 6q was reported by de Grouchy et al ,1 2 at least 23 additional cases have been published. The majority of these cases represent the abnormal segregation of a balanced parental chromosome translocation. While trisomy 6q patients do have some common characteristics, the inconsistent phenotypic features are usually attributed to an accompanying area of monosomy. Most often the deleted area is the terminal band of the recipient chromosome,3-13 although longer deletions have also been reported.14-16 Only deletion of the short arm of acrocentric chromosomes are without clinical effect, as these are the nucleolar organiser regions (NOR) containing the ribosomal genes which are present in multiple copies within the genome. Robertsonian translocation carriers, who lack two NORs, are phenotypically normal. Hence, trisomy 6q patients who lack one NOR2 17-20 can be regarded as cases of “pure” trisomy 6q, together with cases of insertion21 22 and duplication23-25 of 6q material. We report a pair of sibs who carry der(7)ins(7;6)(q21.11;q22.1q23.3)mat, as confirmed by fluorescence in situ hybridisation (FISH). Their phenotypes are compared with other cases of “pure” partial trisomy 6q. Case 1, the proband (II.3, fig 1) is an ethnic Chinese male. He was born at term, weighing 3345 g, to a 32 year old, gravida 7, para 2 female and a 38 year old male. He was referred aged 7 years because of his dysmorphic features and because he was failing in school. The proband's mother had had four spontaneous first trimester miscarriages before the birth of her four children. There was no known consanguinity or previous history of …