SHOX mutations in a family and a fetus with Langer mesomelic dwarfism

Leri-Weill dyschondrosteosis (LWD) and Langer mesomelic dysplasia (LMD) are caused by mutations in the SHOX gene. LWD results from haploinsufficiency and is dominantly inherited, while the more severe LMD results from the homozygous loss of SHOX. We describe a family and fetus with two SHOX mutations. Several relatives carry an approximately 200 kb interstitial deletion that includes the whole SHOX gene. Their condition is mild, with no Madelung deformity, and was originally diagnosed as hypochondroplasia (HCH). This deletion was also transmitted to a female fetus. However, unlike her carrier relatives, the ultrasound scan of the fetus and subsequent autopsy were consistent with LMD. The fetus inherited an additional Xp deletion (Xpter-Xp22.12) that also included the SHOX gene from her chromosomally normal father. This represents a unique molecular condition for LMD: the fetus is a compound heterozygote with two independent deletions, one inherited and one arising from a de novo event

fluorescence, transcription factors, human, dwarfism, x, pregnancy, adult, osteochondrodysplasias, alleles, gene deletion, protein, heterozygote, homozygote, cosmids, proteins, male, musculoskeletal abnormalities, family, diagnosis, metabolism, family health, chromosomes, multiple, laboratories, in situ hybridization, phenotype, research support, fetus, pedigree, report, genetics, female, abnormalities, genetic, humans, autopsy, prenatal diagnosis, non-u.s.gov't, homeodomain proteins, mutation, chondrocytes, polymerase chain reaction, models

10.1002/ajmg.a.30095

1552-4825

179-184

Thomas, N.S.

df2d7c6d-2c96-4aaa-a7ef-7f7987759cf4

Maloney, V.

07e33c11-8048-490b-b93f-ae53f878d002

Bass, P.

3c1b5eca-118b-4ea0-ab63-d545908af425

Mulik, V.

72cc364a-583b-4b89-b7d3-616eca9d1733

Wellesley, D.

17cbd6c1-0efb-4df1-ae05-64a44987c9c0

Castle, B.

1472bdb8-2ec6-4b06-8d62-7a1e6190ca4d

2004

Thomas, N.S.

df2d7c6d-2c96-4aaa-a7ef-7f7987759cf4

Maloney, V.

07e33c11-8048-490b-b93f-ae53f878d002

Bass, P.

3c1b5eca-118b-4ea0-ab63-d545908af425

Mulik, V.

72cc364a-583b-4b89-b7d3-616eca9d1733

Wellesley, D.

17cbd6c1-0efb-4df1-ae05-64a44987c9c0

Castle, B.

1472bdb8-2ec6-4b06-8d62-7a1e6190ca4d

Thomas, N.S., Maloney, V., Bass, P., Mulik, V., Wellesley, D. and Castle, B. (2004) SHOX mutations in a family and a fetus with Langer mesomelic dwarfism. American Journal of Medical Genetics part A, 128 (2), 179-184. (doi:10.1002/ajmg.a.30095).

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Published date: 2004

Keywords: fluorescence, transcription factors, human, dwarfism, x, pregnancy, adult, osteochondrodysplasias, alleles, gene deletion, protein, heterozygote, homozygote, cosmids, proteins, male, musculoskeletal abnormalities, family, diagnosis, metabolism, family health, chromosomes, multiple, laboratories, in situ hybridization, phenotype, research support, fetus, pedigree, report, genetics, female, abnormalities, genetic, humans, autopsy, prenatal diagnosis, non-u.s.gov't, homeodomain proteins, mutation, chondrocytes, polymerase chain reaction, models