Category Archives: Eur J Med Genet

“There is a chance for me” – Risk communication in advanced maternal age genetic counseling sessions in South Africa.

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“There is a chance for me” – Risk communication in advanced maternal age genetic counseling sessions in South Africa.
Eur J Med Genet. 2018 Dec 29;:
Authors: Wessels TM, Koole T
Abstract
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A novel homozygous insertion and review of published mutations in the NNT gene causing familial glucocorticoid deficiency (FGD).

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A novel homozygous insertion and review of published mutations in the NNT gene causing familial glucocorticoid deficiency (FGD).

Eur J Med Genet. 2015 Nov…

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A new mutation for Huntington disease following maternal transmission of an intermediate allele.

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A new mutation for Huntington disease following maternal transmission of an intermediate allele.

Eur J Med Genet. 2015 Jan;58(1):28-30

Authors: Semaka A, Kay C, Belfroid RD, Bijlsma EK, Losekoot M, van Langen IM, van Maarle MC, Oosterloo M, Hayden MR, van Belzen MJ

Abstract
New mutations for Huntington disease (HD) originate from CAG repeat expansion of intermediate alleles (27-35 CAG). Expansions of such alleles into the pathological range (≥ 36 CAG) have been exclusively observed in paternal transmission. We report the occurrence of a new mutation that defies the paternal expansion bias normally observed in HD. A maternal intermediate allele with 33 CAG repeats expanded in transmission to 48 CAG repeats causing a de novo case of HD in the family. Retrospectively, the mother presented with cognitive decline, but HD was never considered in the differential diagnosis. She was diagnosed with dementia and testing for HD was only performed after her daughter had been diagnosed. This observation of an intermediate allele expanding into the full penetrance HD range after maternal transmission has important implications for genetic counselling of females with intermediate repeats.

PMID: 25464109 [PubMed – indexed for MEDLINE]

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Phenotype and Genotype in 103 patients with Tricho-Rhino-Phalangeal Syndrome.

Phenotype and Genotype in 103 patients with Tricho-Rhino-Phalangeal Syndrome.

Eur J Med Genet. 2015 Mar 16;

Authors: Maas SM, Shaw AC, Bikker H, Lüdecke HJ, van der Tuin K, Badura-Stronka M, Belligni E, Bonati MT, Carvalho DR, Cobben J, de Man SA, Den Hollander NS, Di Donato N, Garavelli L, Grønborg S, Herkert JC, Hoogeboom AJ, Jamsheer A, Latos-Bielenska A, Maat-Kievit A, Magnani C, Marcelis C, Mathijssen IB, Nielsen M, Otten E, Ousager LB, Pilch J, Plomp A, Poke G, Poluha A, Posmyk R, Rieubland C, Silengo M, Simon M, Steichen E, Stumpel C, Szakszon K, van den Ende J, van der Steen A, van Essen T, van Haeringen A, van Hagen JM, Verheij JB, Mannens MM, Hennekam RC

Abstract
Tricho-rhino-phalangeal syndrome (TRPS) is characterized by craniofacial and skeletal abnormalities, and subdivided in TRPS I, caused by mutations in TRPS1, and TRPS II, caused by a contiguous gene deletion affecting (amongst others) TRPS1 and EXT1. We performed a collaborative international study to delineate phenotype, natural history, variability, and genotype – phenotype correlations in more detail. We gathered information on 103 cytogenetically or molecularly confirmed affected individuals. TRPS I was present in 85 individuals (22 missense mutations, 62 other mutations), TRPS II in 14, and in 5 it remained uncertain whether TRPS1 was partially or completely deleted. Main features defining the facial phenotype include fine and sparse hair, thick and broad eyebrows, especially the medial portion, a broad nasal ridge and tip, underdeveloped nasal alae, and a broad columella. The facial manifestations in patients with TRPS I and TRPS II do not show a significant difference. In the limbs the main findings are short hands and feet, hypermobility, and a tendency for isolated metacarpals and metatarsals to be shortened. Nails of fingers and toes are typically thin and dystrophic. The radiological hallmark are the cone-shaped epiphyses and in TRPS II multiple exostoses. Osteopenia is common in both, as is reduced linear growth, both prenatally and postnatally. Variability for all findings, also within a single family, can be marked. Morbidity mostly concerns joint problems, manifesting in increased or decreased mobility, pain and in a minority an increased fracture rate. The hips can be markedly affected at a (very) young age. Intellectual disability is uncommon in TRPS I and, if present, usually mild. In TRPS II intellectual disability is present in most but not all, and again typically mild to moderate in severity. Missense mutations are located exclusively in exon 6 and 7 of TRPS1. Other mutations are located anywhere in exons 4-7. Whole gene deletions are common but have variable breakpoints. Most of the phenotype in patients with TRPS II is explained by the deletion of TRPS1 and EXT1, but haploinsufficiency of RAD21 is also likely to contribute. Genotype-phenotype studies showed that mutations located in exon 6 may have somewhat more pronounced facial characteristics and more marked shortening of hands and feet compared to mutations located elsewhere in TRPS1, but numbers are too small to allow firm conclusions.

PMID: 25792522 [PubMed – as supplied by publisher]

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