Tag Archives: #SHOXgene

Reproductive Medicine – Y Chromosome Genetic Diseases

© 2018, GENASSIST, Inc.            

By Keith S. Wexler, MBA, CFO, Business Development Director, GENASSIST, Inc.

Paul Wexler, M.D., F.A.C.O.G., Medical Director, GENASSIST, Inc.

Clinical Professor, Department of OB/GYN, University of Colorado Health Sciences Center

Clinical Professor, Division of Genetics/Dept. of Pediatrics, Univ. of Colorado/The Children’s Hospital

There are many disorders that have been linked to the X chromosome (e.g. hemophilia, some types of muscular dystrophy and male developmental delay.

The Y chromosome is quite small and contains relatively few genes which nonetheless are still very important. Several of the genes are linked to male infertility and spermatogenesis and have been identified on the long arm (q-arm) of the Y chromosome (Yq11.2-11.22) including USP9Y, CDY1, DAZ1, DAZ2, DDX3Y, HSFY1 and RBMY1A1.

The SHOX gene identified on the short arm of both the X chromosome (Xp22.33) and the Y chromosome (Yp11.3) has a role in bone growth and maturation.

Mutations in the SHOX gene have been implicated in shortening of the arms and legs including Langer Mesomelic Dysplasia, Leri-Weil Dyschondrosteosis and Turner Syndrome.

  • The SRY gene (Sex Determining Region on the Y chromosome) is also located on Yp11.3
  • The SOX9 gene on chromosome 17q24.3 is related to the SRY gene and plays a role in bone growth

Swyer Syndrome – a disorder reported in approximately 1:86,000 newborn females also called 46,XY Complete Gonadal Dysgenesis presents with female genitalia and a nonfunctional SRY gene. Mutations in the SRY gene n have been identified in up to 15% of these children who may also present with neuropathy and skeletal abnormalities, usually Campomelic Dysplasia.

Other disorders linked to the Y chromosome include:

  • Retinitis Pigmentosa linked to the RPY gene
  • Jacobs Syndrome (XYY)
  • Hypertrichosis Pinnae (excessive ear hair)

Leri-Weil Dyschondrosteosis

© 2018, GENASSIST, Inc.

By Keith S. Wexler, MBA, CFO, Business Development Director GENASSIST, Inc.

Paul Wexler, M.D., F.A.C.O.G., Medical Director, GENASSIST, Inc.

Clinical Professor, Department of OB/GYN, University of Colorado Health Sciences Center

Clinical Professor, Division of Genetics/Dept. of Pediatrics, Univ. of Colorado/The Children’s Hospital

Leri-Weil Dyschondrosteosis is inherited in an autosomal dominant manner and is due to a deletion or mutation in the SHOX gene, also called the Short Stature Homeobox gene which is on each X chromosome (Xp22.33) and

Y chromosome (Yp11.3).

The SHOX gene plays a major role in stature and development of the skeleton particularly the arms and legs. Both males and females have two copies of the SHOX gene.  The disease is often more severe in females.  A mutation in one of the SHOX genes can cause the disorder. 

Family members affected with Leri-Weil Dyschondrosteosis can have short stature and shortened long bones and each family member can present differently with symptoms from [mild to severe].

As with most autosomal dominant disorders, the severity may be variable and might explain the difference in family members.

It is believed that SHOX gene deficiency is probably more common than previously diagnosed perhaps affecting as many as 1:2000 individuals.

Wrist deformities known as the Madelung Deformity often serves as a clue to a SHOX gene deletion or mutation and is a more severe manifestation of the disorder. 

Other cases with findings similar to Leri-Weil Dyschondrosteosis have been described without evidence of the SHOX gene mutation.

The risk to each child to inherit one X chromosome with the SHOX gene mutation is 1:2 or 50%. Some individuals with the disease will have a SHOX gene mutation on each of their sex chromosomes giving a mother a 100% risk for passing an abnormal gene to all children, male or female.

A SHOX mutation on one X chromosome and the condition in a child inheriting that X chromosome may be variable in severity.

Recommend ultrasound at 4-6 week intervals during the pregnancy to monitor bone growth and evaluate the wrists.

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