Mortlock D P, Innis J W
Dept of Human Genetics, Univ of Michigan Medical School, Ann Arbor 48109-0618, USA.
Nat Genet. 1997 Feb;15(2):179-80. doi: 10.1038/ng0297-179.
There are several human syndromes which involve defects of the limbs and the Müllerian ducts or its derivatives. The hand-foot-genital (HFG) syndrome is an autosomal dominant, fully penetrant disorder that was originally described by Stern et al. Additional reports describing other affected families have also been published. Limb anomalies include short first metacarpals of normal thickness, small distal phalanges of the thumbs, short middle phalanges of the fifth fingers, and fusion or delayed ossification of wrist bones. In the feet, the great toe is shorter due to a short first metatarsal and a small, pointed distal phalanx. Uterine anomalies are common in females with HFG, and typically involve a partially divided (bicornuate) or completely divided (didelphic) uterus, representing defects of Müllerian duct fusion. Urinary tract malformations in affected HFG females include a displaced urethral opening and malposition of ureteral orifices in the bladder wall; affected males may have hypospadias (ventrally misplaced urethral opening) of variable severity. We report the identification of a HOXA13 nonsense mutation in a family with hand-foot-genital syndrome. The mutation converts a highly conserved tryptophan residue in the homeodomain to a stop codon, which truncates 20 amino acids from the protein and likely eliminates or greatly reduces the ability of the protein to bind to DNA.
有几种人类综合征涉及四肢和苗勒管或其衍生物的缺陷。手足生殖器（HFG）综合征是一种常染色体显性、完全显性的疾病，最初由斯特恩等人描述。描述其他患病家族的补充报告也已发表。肢体异常包括厚度正常的第一掌骨短小、拇指远端指骨小、第五指中节指骨短小以及腕骨融合或骨化延迟。在足部，由于第一跖骨短小和远端指骨小且尖，大脚趾较短。子宫异常在患有HFG的女性中很常见，通常涉及部分分隔（双角）或完全分隔（双子宫）的子宫，这代表苗勒管融合缺陷。受影响的HFG女性的泌尿系统畸形包括尿道口移位和输尿管口在膀胱壁中的位置异常；受影响的男性可能有不同严重程度的尿道下裂（尿道口腹侧移位）。我们报告了在一个患有手足生殖器综合征的家族中鉴定出一种HOXA13无义突变。该突变将同源结构域中一个高度保守的色氨酸残基转换为一个终止密码子，该密码子从蛋白质中截短了20个氨基酸，并可能消除或大大降低了蛋白质与DNA结合的能力。
