X-linked isolated growth hormone deficiency (GHD) or combined pituitary hormone deficiency (CPHD), also known as X-linked panhypopituitarism (PHPX), patients with or without intellectual disability¹.

Prevalence

3 families reported, however they were distributed across the world².

Age of Onset

Typical: 0-3 (small sample size)^3,4; range: 0-9³.

HPO Terms

HP:0000821 Hypothyroidism HP:0000824 Decreased response to growth hormone stimulation test HP:0000871 Panhypopituitarism HP:0001256 Mild intellectual disability HP:0001263 Global developmental delay HP:0004322 Short stature

Association

Mendelian

Locus

hg19chrX:139586481-139586526

hg38chrX:140504316-140504361

t2tchrX:138816203-138816248

Details

Expansion to 22-26 repeats or contraction to 8 repeats can cause disease, as reported in 3 families⁵. There is phenotypic and allelic overlap between XLID and PHPX, with the pathogenic threshold for XLID estimated at 26 motifs and the pathogenic threshold for PHPX estimated at 22 motifs^6,7.

Mechanism

LoF

Polyalanine expansions leading to aggresome formation and impaired transcriptional activity⁸.

Detection

Year

2002⁷

Location in Gene

Coding Exon 1

Gene Strand

Alleles

Ref. Motif

GCN

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

NGC

Pathogen. (gene)

GCN

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

–

Interrup. (gene)

–

References

Direct supporting references for info on this page.

A novel mutation in SOX3 polyalanine tract: a case of Kabuki syndrome with combined pituitary hormone deficiency harboring double mutations in MLL2 and SOX3.

Masaki,Takagi, Tomohiro,Ishii, Chiharu,Torii, Kenjiro,Kosaki, Tomonobu,Hasegawa

Pituitary · 2014-12-01

pmid:24346842

2omim:300123

X-linked isolated growth hormone deficiency: expanding the phenotypic spectrum of SOX3 polyalanine tract expansions.

Emma M M,Burkitt Wright, Rahat,Perveen, Peter E,Clayton, Catherine M,Hall, Teresa,Costa, Annie M,Procter, Carol A,Giblin, Dian,Donnai, Graeme C,Black

Clinical dysmorphology · 2009-10-01

pmid:19654509

Increased transactivation associated with SOX3 polyalanine tract deletion in a patient with hypopituitarism.

Kyriaki S,Alatzoglou, Daniel,Kelberman, Christopher T,Cowell, Rodger,Palmer, Ivo J P,Arnhold, Maria E,Melo, Dirk,Schnabel, Annette,Grueters, Mehul T,Dattani

The Journal of clinical endocrinology and metabolism · 2011-02-02

pmid:21289259

Resources for Genetics Professionals — Genetic Disorders Caused by Nucleotide Repeat Expansions and Contractions

Stephanie E.,Wallace, Lora JH,Bean

GeneReviews® [Internet] · 2022-10-20

genereviews:NBK535148

Over- and underdosage of SOX3 is associated with infundibular hypoplasia and hypopituitarism.

Kathryn S,Woods, Maria,Cundall, James,Turton, Karine,Rizotti, Ameeta,Mehta, Rodger,Palmer, Jacqueline,Wong, W K,Chong, Mahmoud,Al-Zyoud, Maryam,El-Ali, Timo,Otonkoski, Juan-Pedro,Martinez-Barbera, Paul Q,Thomas, Iain C,Robinson, Robin,Lovell-Badge, Karen J,Woodward, Mehul T,Dattani

American journal of human genetics · 2005-03-30

pmid:15800844

Transcription factor SOX3 is involved in X-linked mental retardation with growth hormone deficiency.

Frédéric,Laumonnier, Nathalie,Ronce, Ben C J,Hamel, Paul,Thomas, James,Lespinasse, Martine,Raynaud, Christine,Paringaux, Hans,Van Bokhoven, Vera,Kalscheuer, Jean-Pierre,Fryns, Jamel,Chelly, Claude,Moraine, Sylvain,Briault

American journal of human genetics · 2002-11-08

pmid:12428212

Polyalanine expansion mutations in the X-linked hypopituitarism gene SOX3 result in aggresome formation and impaired transactivation.

Jacqueline,Wong, Peter,Farlie, Sebastien,Holbert, Paul,Lockhart, Paul Q,Thomas

Frontiers in bioscience : a journal and virtual library · 2007-01-01

pmid:17127446