A complex phenotype in a family with a pathogenic SOX3 missense variant

TY - JOUR

T1 - A complex phenotype in a family with a pathogenic SOX3 missense variant

AU - Jelsig, Anne M

AU - Diness, Birgitte R

AU - Kreiborg, Sven

AU - Main, Katharina

AU - Larsen, Vibeke A

AU - Hove, Hanne

N1 - Copyright © 2017. Published by Elsevier Masson SAS.

PY - 2018/3

Y1 - 2018/3

N2 - Duplications and deletions of Xq26-27 including SOX3 (Xq27.1) have been associated with X-linked mental retardation and isolated growth hormone deficiency (OMIM 300123) or X-linked panhypopituitarism (OMIM 312000). Yet, pathogenic point mutations seem to be extremely rare. We report a family with three affected males with several clinical features including mild intellectual disability, microphthalmia, coloboma, hypopituitarism, facial dysmorphology and dental anomalies, including microcephaly, retrognathia and a solitary median maxillary central incisor amongst other features. Using Whole Exome Sequencing a missense variant in SOX3, NM_005634.2:c.449C>A; p.(Ser150Tyr) was identified. Segregation analysis in the family demonstrated that the variant was inherited through healthy females with its origin in the maternal grandmother showing germline mosaicism. Thus, we report one of the first cases of a pathogenic variant in SOX3 and germline mosaicism of this variant.

AB - Duplications and deletions of Xq26-27 including SOX3 (Xq27.1) have been associated with X-linked mental retardation and isolated growth hormone deficiency (OMIM 300123) or X-linked panhypopituitarism (OMIM 312000). Yet, pathogenic point mutations seem to be extremely rare. We report a family with three affected males with several clinical features including mild intellectual disability, microphthalmia, coloboma, hypopituitarism, facial dysmorphology and dental anomalies, including microcephaly, retrognathia and a solitary median maxillary central incisor amongst other features. Using Whole Exome Sequencing a missense variant in SOX3, NM_005634.2:c.449C>A; p.(Ser150Tyr) was identified. Segregation analysis in the family demonstrated that the variant was inherited through healthy females with its origin in the maternal grandmother showing germline mosaicism. Thus, we report one of the first cases of a pathogenic variant in SOX3 and germline mosaicism of this variant.

KW - Journal Article

U2 - 10.1016/j.ejmg.2017.11.012

DO - 10.1016/j.ejmg.2017.11.012

M3 - Journal article

C2 - 29175558

SN - 1769-7212

VL - 61

SP - 168

EP - 172

JO - European Journal of Medical Genetics

JF - European Journal of Medical Genetics

IS - 3

ER -